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The AF Report
Atrial Fibrillation: Preventing A Stroke Crisis
A report for patients and
those who care for them
A report for healthcare
professionals
A report for policy
makers and purchasers
www.preventaf-strokecrisis.org
An expert report on how we can prevent AF from causing a deadly UK stroke crisis
www.afa.org.uk
Table of contents
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Report summary
4
Call to action
5
Chapter 1 - What is AF?
?
8
Chapter 2 - What is a stroke?
?
12
Chapter 3 - Why does AF matter?
?
17
Chapter 4 - Cost of AF to individuals and society?
?
19
Chapter 5 - Who is at risk of AF?
?
22
Chapter 6 - Treating AF and preventing stroke
26
Chapter 7 - The importance of guidelines
31
Chapter 8 - Current challenges
36
Chapter 9 - New treatments in development
41
References
45
The AF Report
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Report summary
We are in the midst of a silent epidemic. Failure to
act now will result in a crisis that we cannot afford.
The epidemic results from atrial fibrillation (AF), a
heart rhythm disorder that causes strokes. Strokes,
in turn, cause death and disability. Stroke is the
brain’s equivalent of a heart attack and it afflicts
one person every five minutes in the UK1 and it is
also a leading cause of adult disability.2,3
To prevent the tragic consequences of this epidemic it is
essential that we target the prevention of stroke among
the rapidly growing number of people who have AF.
Atrial fibrillation, the most common heart rhythm disorder, is less well known than stroke but it affects an
estimated 1.5 million people in the UK. Aside from
many other symptoms and consequences, people with
AF become five times more likely to suffer a stroke.68 AF
prevents blood flowing properly through the heart. This
disruption allows clots to form. The most common and
damaging type of stroke results from clots that have
travelled to the brain where they cause a blockage in a
blood vessel. Twenty percent of all strokes of this type of
stroke result directly from AF. 4
Moreover, AF-related strokes are more severe and cause
greater disability than strokes in patients without AF.4,5
Half of all AF patients will fail to survive more than
12 months following a stroke.4 For many sufferers,
surviving a stroke can be worse than dying; as disability
and fear of death become constant companions.
AF and stroke not only devastate patients’ lives,6
but also the lives of their families and carers.7
Despite the availability of free and simple checks, authoritative estimates suggest around half of AF patients
remain undetected. This is frequently because patients
are unaware that the symptoms they experience are a
sign of anything serious.8,10 Tragically, for many people a
stroke is the first sign of underlying AF.
There remains an extremely low level of patient awareness of AF and stroke.9 Education is needed on the signs
and symptoms of AF, on how AF is related to stroke, as
well as on the risks they present both to life and health.
The current epidemic is predicted to worsen as the
number of people with AF is expected to more than
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double by 2050.11,12 AF affects a greater proportion of
older people than younger. Unless we take action, our
ageing population will increase both the number of people with AF and the number of strokes that result from
AF.13 This increase will also be amplified as we become
better at preventing deaths from other conditions, such
as heart attacks, which themselves increase the risk of AF
developing.14
Properly used, existing treatments are effective and could
prevent AF-related strokes, saving thousands of lives
and millions from the National Health Service (NHS)
budget.68 For example, when anticlotting therapy is used
appropriately it is highly effective; lowering stroke risk by
about two-thirds in AF patients.73
Yet, despite the existence of effective guidelines, vital
anticlotting treatments are both underused and misused
in clinical practice.15,16 This is largely due to perceived
drawbacks16,5 associated with the most commonly used
anticoagulant drug, warfarin.17,18 The impacts of warfarin on blood clotting need to be monitored not only to
ensure that the drug is working, but also to ensure that
the risk of excessive bleeding doesn’t become unacceptably high. The need for monitoring and the risk of bleeding appear to have a disproportionate impact on the use
of effective anticlotting therapy that would otherwise save
thousands of lives.
There is evidence that the above perceived drawbacks
frequently overshadow current guidelines. This results
in many doctors sticking with out-of-date treatment
advice19,20,125,21 despite compelling evidence that following current guidelines dramatically reduces death and
disability.
Today, many thousands of preventable strokes occur
every year leading both to thousands of early deaths and
a devastating burden on individuals, families and society.
This burden takes many forms including disability,
healthcare costs, social care as well as loss of working
hours and tax revenues.
There is therefore an urgent need for coordinated action
within the NHS to achieve earlier diagnosis and better
management to reduce the risk of stroke in patients with
AF. To address this need, six actions called for by the
AFA and ACE are explained in the next section.
The AF Report
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Call to action
AntiCoagulation Europe (ACE), the Atrial Fibrillation
Association (AFA), and all those who endorse the
recommendations in this report, call for an urgent
focus on AF within the National Health Service
(NHS), and call specifically for six actions that will
improve and extend the lives of UK AF patients. If
implemented, these actions will prevent thousands
of fatal and debilitating cases of stroke; saving
hundreds of thousands from stretched healthcare
budgets.
Budgetary pressures within the NHS are ever-present
and inevitable. Moreover, financial pressure demands
sound reasoning and compelling arguments before
policy change or new services. Given the weight of the
evidence collated in this report, it is clear that the opportunity exists to make considerable long-term cost savings
by implementing policies that today will result in the improved detection, diagnosis and management of patients
with atrial fibrillation to prevent stroke.
Six actions
To achieve these goals, the six actions called for
by the AFA and ACE are:
• Targeted screening:
The introduction of a targeted national screening
programme drawing on routine manual pulse
checks and ECG readings
• Guideline adherence:
The development and adoption of policies that
increase GP motivation to follow international
guidelines
• Public awareness, patient empowerment:
The use of existing materials to fuel a national public
and patient education campaign to improve detection
and patient empowerment
• Equity of treatment:
The imposition of equal access to AF treatments and
services for all patients using the NHS regardless of
location
The AF Report
• GP education:
An AF education campaign for GPs to illustrate the
importance of symptomatic control, appropriate
referral and the value of patient empowerment
• AF research:
Government support for research into the causes,
prevention and treatment of AF
Targeted screening
We call for the introduction of a targeted national
screening programme drawing on routine manual
pulse checks and ECG readings
The prevalence of AF in our society continues to grow,
but measures to detect and diagnose these patients
remain insufficient. Consequently, there are many hundreds of thousands of patients with AF who are currently
unaware, untreated and at substantially elevated risk of
suffering a stroke. Moreover, the early diagnosis of AF is
associated with an increased range of treatment options,
some of which have been demonstrated to eliminate AF
permanently.
A simple route to improving early detection and
management of AF patients is through the introduction
of an effective national AF screening programme.
In chapter five of this report, the potential advantages of
routine screening methods are clearly outlined. For these
to be effective, a nationwide policy change is required,
one which requires:
• The audit of all patients in general practice to
determine and flag those at AF and stroke risk
•
Manual pulse checks for all risk-flagged patients
when visiting their local GP surgery
• Immediate access to an ECG for all flagged
patients for whom AF is suspected
• Ready access to 24 and 48-hour heart monitoring
to secure a diagnosis of intermittent AF
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Guideline adherence
We call for the development and adoption of policies
that increase GP motivation to follow international
guidelines
Evidence discussed in chapter seven of this report illustrates that the following of guidelines is associated with
improved patient treatment and a reduction in stroke.
Confusingly in the UK, physicians have to draw upon two
sets of conflicting guidance: the 2006 guidance from the
National Institute for Health and Clinical Excellence
(NICE) which all doctors in England and Wales are
expected to follow; and the 2010 guidelines from the
European Society of Cardiology (ESC) which represent
the most current expert consensus on the affective
management of patients with AF.
The existing NICE guideline for AF (CG36) is currently
under review. The AFA and ACE have formally voiced
their support for this review and look forward to engaging
in consultation with NICE to ensure a revision that will
result in harmony with European guidelines and the
effective treatment of as many AF patients as possible.
Specifically we call for accelerated review of the NICE
clinical guideline on AF and for:
• NICE adoption of the treatment recommendations in
the ESC 2010 guidelines
• NICE adoption of patient risk calculations using
CHADS2 and CHA2DS2VASc as described in the
ESC 2010 guidelines
• NICE recommendation of a national opportunistic
screening programme based upon the flagging of
suitable patients, routine manual pulse checks and
immediate access to ECG checks
• NICE recommendation for early referral to an
appropriate specialist when many patients might be
suitable for ablation and anti-arrhythmic therapy
• Replacement of the traditional but arbitrary
classification of AF (based upon the duration of AF
episodes) for treatment decisions
We call for changes to the GP payment system to increase
patient treatment in accordance with international guidelines.
General practitioners are also currently poorly motivated
by payments through the Quality Outcomes Framework
(QOF) to manage AF patients in accordance with
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guidelines. QOF seeks to reward
doctors
for the
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achievement of certain targets. The current system pays
extra to doctors if they treat AF patients only with aspirin,
despite considerable evidence that a significant
additional reduction in risk of stroke is possible with anticoagulation treatment. Importantly, these data also show
that the advantages of warfarin over aspirin come
without a significant increase in the risk of bleeding.
At the time of preparation of this report, a revision to
QOF has been proposed. We strongly support the rapid
adoption of these revisions:
• Reward for a high proportion of AF patients for whom
a formal stroke risk has been calculated
• Reward for a high proportion of AF patients receiving
anticoagulation therapy
Public awareness, patient
empowerment
We call for the use of existing materials to fuel a
national public and patient education campaign to
improve detection and patient empowerment
The importance of public and patient awareness and
knowledge cannot be over-stressed. Almost anyone can
perform a simple pulse check if they want to check for
the possibility that they have AF. We have also reviewed
evidence in chapter eight that greater treatment success
is achieved in patients who have sufficient knowledge of
their condition to contribute to treatment decisions and
targets.
Yet, today, not only are there many thousands of patients
unaware that they currently have AF, many of those who
have been diagnosed are unaware of what is wrong with
their heart or why they are taking medication.
ACE and the AFA have developed a wealth of patient
information, much of which could provide source
material for a national public and patient awareness and
education campaign. We call for Department of Health
engagement in and support of these campaigns to:
• Increase patient awareness of AF, its signs and how
they can check for AF and their risk of stroke with
simple checks and tests
• Increase routine supply of educational material at the
point of diagnosis, and from then on, so that patients
can gain sufficient knowledge to engage in treatment
decisions
The AF Report
www.afa.org.uk
Equity of treatment
We call for the equal access to AF treatments and
services for all patients using the NHS regardless of
location
The simple presence of conflicting clinical guidelines
leads inevitably to the unequal treatment of AF patients
within the NHS. This is by no means the only cause of
inequity for AF patients; many are reviewed in chapter
eight of this report. By having the NHS, a single body
responsible for almost all UK healthcare, we have an
unparalleled opportunity to ensure that efficient and
effective treatments and services are provided to all UK
citizens regardless of local circumstances. Constant
vigilance is required to identify and eliminate inequities
for patients in the NHS but several targets for attention
can easily be identified. We call for government policy
and medical practice that ensures:
• Equity of guideline adherence among doctors
• Equity of access to services such as anticoagulation
clinics
• The definition and implementation of minimum
standards to eliminate or improve services and
treatments that fall short of what patients deserve
• Equity of treatment decisions based on clinical status
not arbitrary definitions or timing
• Equity of access to anticoagulation treatment
regardless of location of the patient or the availability
of local anticoagulation services
• Equity of access to ideal referral opportunities
regardless of the location of the patient or the
availability of local heart rhythm specialists
GP education
We call for an AF education campaign for GPs to
illustrate the importance of symptomatic control,
appropriate referral and the value of patient
empowerment
In chapters seven and eight of this report, we document
many instances where doctors over-look symptoms,
under-use treatments and where they fail to interpret
correctly the amount of risk that a patient is willing to
accept for a given benefit.
Patients suffering from the symptoms of AF can benefit
significantly from early diagnosis and referral for treatments
that can have a significant positive impact. It is important
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that GPs develop an understanding
of
how
signifi
cant
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these symptoms are for the patient, and how effectively
they can be helped once diagnosed and referred for
specialist treatment.
We have also reviewed extensively, in chapter seven of
this report, the discrepancies between the theoretical
benefits of anticoagulation treatment and the actual
benefit achieved in routine clinical practice. Much of this
difference can be accounted for by deviation from guidelines founded on a misunderstanding among physicians
of how their patients view the risks and benefits of treatment.
The above challenges can be met with educational efforts
and tools that:
• Improve GP understanding of the impact that AF
symptoms have on quality of life
• Improve GP understanding of the benefits of patient
education and engagement in decisions
• Help GPs improve patient understanding of the risks
and benefits of treatment
• Improve GP understanding of the potential benefits of
early referral
AF research
We call for government support for research into
the causes, prevention and treatment of AF
Many of the challenges faced by healthcare policy makers
and doctors today arise from inadequate access to the
necessary data to make effective decisions. This report
and the document upon which it is based aim to help
increase access to vital information. However, some
data simply doesn’t yet exist, highlighting an urgent need
for continued research into AF so that services and
policies can be developed with a firm confidence of
success and cost effectiveness for the NHS. To this end,
we call for government support for:
• An assessment of the burden and severity of disease
for all patients with AF, based on patient experience
and the impact on their quality of life
• Research to identify patients at risk of AF and AFrelated stroke, and the likely impact of existing and
new therapeutic approaches to the management of
AF
• Multi-national registries and monitoring studies to
evaluate the effect of interventions to manage AF and
prevent AF-related stroke.
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Chapter 1 - What is AF?
Key points
• AF is the most common sustained heart rhythm
disorder
• Having AF doubles the risk of death, regardless
of age
• In symptomatic patients, AF is frequently
associated with a highly significant reduction in
quality of life
• In all AF patients, the risk of suffering a stroke is
increased nearly 500%
• AF can be detected with a simple pulse check
but approximately half of all patients remain
undiagnosed
• AF, and AF related illness, costs the NHS over
£2.2 billion each year
• AF affects nearly 2% of the population,
a number that is rising fast
• Between 100,000 and 200,000 people in the
UK develop AF every 12 months
Atrial fibrillation (AF) is a common heart rhythm disorder
associated with deadly and debilitating consequences
including heart failure, stroke, poor mental health, reduced quality of life and death.71
AF is also the most prevalent sustained heart rhythm
disorder.193 Today, approaching a million Britons are
diagnosed with AF,61 yet experts suggest that between
one third and a half of all AF patients have not yet been
detected. Today, everyone aged 40 or over has a life
time risk of developing AF of at least one in four.24 For
context, this compares with one in eight for breast cancer
in women of the same age.25
Among many damaging and debilitating consequences,
AF increases an individual’s risk of suffering a stroke by
five times.68 This effect alone results in considerable
disability and death,193,4 not to mention avoidable millions in healthcare expenditure61 that the National Health
Service (NHS) cannot afford.
8
What is AF?
Atrial: pertaining to the atria (pleural of atrium) the
top two chambers of the heart
Fibrillation: the rapid, irregular and unsynchronised
contraction of muscle fibres
AF is a heart rhythm disorder (a cardiac arrhythmia) of
the atria. The normal beat of the heart (called sinus
rhythm) is managed by a sophisticated electrical control
system. This system matches heart rate with physiological demands and ensures that the four chambers of
the heart contract and relax in time with one another to
maintain a steady and efficient rhythm to pump blood.
The heart’s natural pacemaker is a cluster of special
cells in the atria called the sinus node. The sinus node
controls the rate at which the atria contract and relax. In
AF, chaotic electrical activity develops in the walls of the
atria, over-riding the sinus node. The normal, steady
rhythm of the atria is disrupted and they instead begin to
fibrillate; quivering with a shallow but very fast rhythm as
their muscular walls fail to contract with regularity and
coordination.
An irregular pulse
This atrial fibrillation disrupts the electrical signals that
trigger the contraction of the heart’s main pumping
chambers, the ventricles. Consequently, the ventricles
beat faster and their rhythm becomes irregular as the
electrical conduction system is over-run by the fast and
chaotic impulses from the fibrillating atria. This altered
ventricular beating can be detected as an irregular
pulse, a valuable yet simple test for AF.
A progressive condition
Initially for most patients, AF is an electrical problem
in the heart that can be addressed by therapies which
treat the rate and rhythm of the heartbeat, or which can
immediately return the heart to normal sinus rhythm – a
procedure called cardioversion.
The AF Report
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AF increases the risk of stroke by nearly five times, more than any other cardiovascular
risk
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Increases stroke
risk by 430%
Incidence of stroke
50
40
30
20
Increases stroke
risk by 340%
Increases stroke
risk by 240%
10
0
High blood
pressure
Without this condition
With this condition
Coronary artery
disease
Heart failure
AF
Risk factors for stroke
Over time, AF which is untreated, or which fails to
respond to treatment, begins to change the anatomy of
the heart muscle, interfering further with the electrical
conduction necessary for a normal heart beat. Eventually, all treatments to correct the electrical system become
ineffective, leading to therapy that aims only to prevent
the consequences of AF.
Deadly consequences
Atrial fibrillation disrupts the efficient pumping of blood
through the heart and around the body. The disturbance
in flow can allow clots to form where the blood moves
too slowly. The blood stream can then carry these clots
to vessels in the brain causing deadly blockages that
result in stroke.
Massive NHS burden
AF is a significant and growing drain on the NHS.
During the past 20 years there has been a 60% increase
in the number of patients being admitted to hospitals
as a result of AF.26 In 2008, there were an estimated
850,000 GP visits because of AF in the UK.61 When
including AF as a causative secondary diagnosis, the
total cost of AF to the NHS has been calculated to be
nearly £2.2 billion a year.61 Some authoritative estimates
predict a three-fold increase in AF over the next
50 years.12,27
The AF Report
Increases stroke
risk by 480%
Signs, symptoms and consequences of
AF
There are many negative consequences of AF frequently
leading sufferers into a life of confusion and despair.28
AF is associated with a significant increase in risk of
stroke, heart failure and death.71 It has also been found
that approximately one third of AF patients suffer persistent anxiety or depression. From the same research,
depression was also noted to have considerable negative impact on future quality of life.29 Other symptoms
include palpitations, shortness of breath, light-headedness, fainting, fatigue and chest pain.33 For emergency
admissions to hospital, AF most often presents as difficulty with breathing, chest pain and palpitations.64
A simple and easily identifiable sign of AF is an irregular pulse. For this reason, many AF experts and patient
advocacy groups are calling for pulse checks to become
a free, swift and routine part of every GP visit.
However, AF is frequently intermittent and many people with AF have no or non-specific symptoms.8 These
combine to make detection and diagnosis difficult; often,
AF is not apparent until a person goes to see their doctor
with a serious complication such as stroke, a blood clot
in the leg or heart failure.64
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Yet, even patients who do experience symptoms of AF
are not always diagnosed immediately. In a recent
international survey, there was an average delay of
2.6 years between the onset of symptoms and the
diagnosis of AF.30 In another piece of research, among
patients with documented chronic AF, it was found that
more than a third were not aware of their diagnosis and
up to half were unaware of why they were being treated.31 This indicates that many patients with AF are not
being detected or managed effectively and that many
are at risk of serious long-term consequences such as
stroke.
Efforts have already begun to increase the rates of
diagnosis and effective management of AF. For example, the National Institute for Health and Clinical Excellence (NICE) recommends that doctors make assessments for the presence of AF in all people presenting
with breathlessness, palpitations, fainting/dizziness, chest
discomfort, stroke or mini-stroke (TIA).32
How does AF lead to stroke?
AF results in a fivefold increase in the risk of stroke,
making it the most powerful independent risk factor for
stroke.68 Moreover, strokes in patients with AF tend to be
more severe than in non-AF patients.72 The above chart
illustrates the impact that AF has on the likelihood of
suffering a stroke compared to other stroke risk factors
such as high blood pressure, heart disease and heart
failure.
The risk of stroke increases because AF is associated
with the formation of clots inside the heart. During AF,
blood can slow as fibrillation prevents the normal highpressure flow of blood through the heart and out to the
arteries. When blood is allowed to travel slowly the
natural formation of clots can begin. This is usually a
safety mechanism to help prevent excessive bleeding at
sites of injury.
In stark contrast, clots forming within the heart and
arteries can be deadly. As clots travel downsteam into
increasingly smaller arteries, even small clots can cause
blockages that prevent oxygen and nutrients reaching the
tissues. If such a blockage occurs in the brain, the
damage done by the lack of blood flow results in a stroke.
AF is estimated to be responsible for approximately
15%-20% of all strokes. 63,4
Who gets AF?
It is difficult to overstate just how big a problem AF
presents. To provide some perspective, one authoritative
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and recent study from the Mayo
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concluded that, for anyone aged 40 or above, the lifetime risk of AF exceeds 25%;24 meaning that one in four
adults can expect to develop AF. This compares to the
lifetime risk of breast cancer in women of the same age,
which is one in eight.25 However, because of improved
detection methods, each new study of the prevalence of
AF reports an increase for the same point in time. For
example, the Mayo clinic study above was published in
2004 when AF was thought to affect less than 1% of the
population they were studying.34
We now know that around 2% of the population in 2004
had AF. It is predicted that by 2050, over 4% of the
population will have it.12 Consequently, it is very likely
that, for those aged 40 today, the lifetime risk of developing AF in fact higher than one in four .
Given the number of people who have or will develop
AF, it is not easy to define a typical AF patient. Men and
women of all ages can be affected. In general terms,
the likelihood of developing AF increases with age.193
However, some people appear to be at a higher
genetic risk. This predisposition to AF is most often seen
in young patients.191,199 In addition, some studies
suggest that the incidence of AF is higher than normal
in athletes and others who engage in frequent, vigorous
exercise regardless of age.35,36 For all these reasons, AF
is not just a condition of the elderly.
What causes AF?
The most common underlying causes of AF are high
blood pressure, thyroid disease and, to a lesser extent,
coronary artery disease and diabetes.195,178 Dietary,
lifestyle and other factors that contribute to the risk of AF
include emotional and physical stress and excessive
caffeine, alcohol or illicit drug intake.64
The main causes of AF are different than they were
20 years ago. At that time, rheumatic disease
commonly resulted in the hardening and narrowing of
the heart’s mitral valve (mitral stenosis) and was an
important cause of AF. The incidence of rheumatic
disease in European patients has diminished considerably in recent decades due mainly to improved living
conditions. Today, AF as a result of mitral stenosis is
relatively rare. The term ‘non-valvular AF’ is used to
describe cases where rhythm disturbance is not
associated with these problems.8 This report is
concerned only with non-valvular AF, which is that
most frequently encountered in the UK.
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How many people suffer from AF?
As we have seen, AF is responsible for many hundreds of
thousands of GP visits61 despite estimates that nearly between one third and a half of those affected are yet to be
diagnosed. Over 800,000 patients in the UK are known
to have AF.61 As symptoms are not always specific, and
because there is no routine screening for early detection,
experts estimate that the total number with AF in the UK
might exceed 1.5 million.
The numbers of people affected by a condition are generally measured in two ways. Prevalence is the proportion of a population affected at any given time; usually
as a percentage. The other measure is incidence, which
measures just the newly affected patients in the population over a given time span, usually 12 months.
Growing and under-detected
prevalence of AF
As seen in the example above from the Mayo clinic in the
US, the proportion of the UK population with diagnosed
AF is also growing. Today we believe the prevalence of
AF in the UK to be near 2% and increasing.27 Between
1994 and 2006, the UK prevalence of AF rose from
0.78% to 1.42%.27 This increase appears to reflect
increasing life expectancy as well as the impact of medical science that enables more people to survive conditions such as heart attacks that can add to the likelihood
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also the020
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likelihood
that an improved focus on AF, and improved methods of
detection, will uncover greater numbers still.
Independent of this increase in prevalence of AF over
time in our society, the number of people with AF has
been shown to double with each advancing decade of
age, from 0.5% at age 50-59 years to almost 9% at
age 80-89 years.193 Not surprisingly, the incidence of
AF also increases with age, contributing to the growing
prevalence.193
As all these factors combine, it has been predicted that the
total number of people affected by AF is likely to triple by
2050.12,27
Incidence of AF in the UK
The most recently published data on the number of
people in the UK who develop AF is from 2002. This
research reported that the incidence of AF in the UK was
1.7 per 1,000 patient years.37 With today’s population
this would mean that 105,000 people develop AF every
year. If, however, the number of people developing AF
has been increasing each year since 2002, similar to the
increase observed above, then it could be that
approaching 200,000 people in the UK are now
developing AF every 12 months.37,12
The number affected by AF is predicted to double by 205011
7.0
Millions of adults with AF
6.0
5.0
4.0
3.0
2.0
1.0
0
1990 1995 2000 2005 2010 2015 2020 2025 2030 2035 2040 2045 2050
Year
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Chapter 2 - What is stroke?
Key points
• Stroke accounts for 10% of all deaths
• Stroke affects 150,000 people in the UK, killing
53,000 each year
• Stroke-related costs in the UK NHS amount to
£2.8 billion
• Surviving a stroke is frequently reported to be
‘worse than death’
• Stroke is a leading cause of adult disability
• The consequences of stroke are dramatic and
can negatively impact many people beyond the
stroke victim
The brain requires a constant supply of blood for it to
receive essential oxygen and nutrients. A stroke happens
when the blood supply to any part of the brain is cut off
and brain tissue is damaged.
The impact of a stroke is both instant and unpredictable.
The nature and the severity of the effects depend on the
amount of damage caused and the part of the brain that
has been affected. Frequently people become paralysed,
numb or incapable of normal speech. Vision can be
impaired, as can both thoughts and feelings.
Stroke accounts for 10% of all deaths,43,56 and is also a
leading cause of adult disability.3,38 The sudden nature of
stroke means that sufferers, families and carers have no
opportunity to prepare for what is usually a tremendous
blow to their lives.
Beyond the personal impact of death and disability,
stroke costs us all through the massive burden it places
on National Health Service (NHS) budgets and the
impact it has on the wider economy. It is estimated that
the direct cost of stroke to the NHS is £2.8 billion, and
that stroke patients occupy up to a quarter of all hospital
beds.3
Effective methods to prevent stroke in people at high risk
are both widely available and inexpensive. The potential
exists to save thousands of lives and millions from healthcare budgets.
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What causes a stroke?
The vast majority, around 85%, of strokes are caused
by a blockage in one of the blood vessels that supplies
the brain.56 The remaining 15% are usually the result
of a bleed. Strokes caused by blockages are called
ischaemic (ISS-KEEM-IC). Ischaemic is a medical term
denoting a lack of oxygen. The most common cause
of ischaemic strokes is a blockage caused by a blood
clot. Most ischaemic strokes are the result of an embolism, which is a clot, or other material, that travelled to
the brain in the bloodstream from somewhere else. For
example, a blockage caused by a clot that formed in
the heart is a cardioembolic ischaemic stroke. Strokes
caused by bleeds are called haemorrhagic (HEM-UHRA-JIC).
What’s a mini-stroke or TIA?
If the blood supply to the brain is only briefly interrupted
a mini-stroke might result. Also known as a transient
ischaemic attack or TIA. The symptoms of a TIA are very
similar to those of a stroke but last fewer than 24 hours.
It is vital that medical attention is sought regardless of the
temporary effects; individuals who have had a TIA are at
high risk of suffering a stroke. Studies have shown that
in the 90 days following a TIA, the risk of stroke exceeds
10%.39
How many people does stroke affect?
Worldwide, stroke is the most common cardio-vascular
disorder after heart disease, accounting for 5.7 million
deaths annually, nearly one in ten of all deaths.43 In the
UK, 150,000 people are struck by stroke each year,1 and
53,000 people are killed.40 This makes stroke the third
biggest killer in the UK after heart attacks and cancer.41
Stroke accounts for 9% of all deaths among UK men and
13% among UK women.42
For many, surviving a stroke is a fate worse than death;
stroke is the leading cause of adult disability. Over
300,000 people in the UK are living with permanent
disabilities as a result of suffering a stroke.3
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The total number of people living through the consequences of stroke in Europe has been estimated to be
9.6 million.43 A World Health Organization (WHO)
study reported that the annual number of new cases in
Europe to be two million in 2004.43 This was comparable to the estimated annual incidence of cancer cases at
2.9 million for the same year.44
For countries within the EU, a study based on data from
WHO estimated the number of strokes to be 1.1 million in 2000.69 Furthermore, it has been predicted that
stroke incidence will increase to 1.5 million per year
by 2025, largely owing to the increasing proportion of
elderly individuals.69
The below charts illustrate authoritative estimates of
stroke incidence throughout Europe. It is immediately
apparent from the first chart that some countries face a
greater challenge than others and that, Europe-wide,
men are generally affected more than women. It is
also clear that the UK has a long way to go if we are to
reduce the rate of stokes to levels currently observed in
France and Switzerland. Unless we act now to prevent
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immeasurably more difficult.
This second chart shows the same data by age. While it
is clear that stroke is most commonly an affliction of the
elderly, there are many countries within which a disproportionate number of those affected by stroke are aged
55-74.
Who suffers from stroke
While predominantly affecting the elderly, approximately
25% of strokes occur in people aged below 65 years.22
In the UK, it has been estimated that 20,000 strokes
occur in those who are 45 and younger every year.
Several risk factors other than age contribute significantly
to stroke risk. Principal among them are atrial fibrillation, heart failure, heart disease and high blood pressure. Atrial fibrillation has the most powerful impact,
elevating risk over a non-AF patient by five times. AF
is directly responsible for 20% of strokes. High blood
Comparing stroke rates in Europe.69
Latvia
Portugal
Greece
CzechRepublic
Estonia
Hungary
Slovenia
Lithuania
Luxembourg
Italy
Malta
Cyprus
Poland
Finland
Norway
Germany
Ireland
Austria
UK
Sweden
Denmark
Iceland
Netherlands
Belgium
Slovakia
Spain
France
Switzerland
Women
Men
Total stroke
0
5000
10000
15000
20000
25000
Estimated numbers of strokes as a proportion of population
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The risk of stroke generally increases with age.69
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Latvia
Portugal
Greece
CzezhRepublic
Estonia
Hungary
Slovenia
Lithuania
Luxembourg
Italy
Malta
Cyprus
Poland
Finland
Norway
Germany
Ireland
Austria
UK
Sweden
Denmark
Iceland
Netherlands
Belgium
Slovakia
Spain
France
Switzerland
75+
55-74
25-54
Total stroke
0
5000
10000
15000
20000
25000
Estimated numbers of strokes as a proportion of population
pressure on its own elevates the risk less than each of
the other three main risk factors, but because so many
people have high blood pressure, it represents the single
biggest cause of stroke in the UK.
Lifestyle factors also play an important role. Smoking
has been shown to double a person’s risk of suffering a
stroke. Poor diet, lack of exercise and excessive alcohol
intake have also been shown to increase stroke risk.
Some ethnic differences may also exist, reflecting differences in the predisposition to some of the risk factors
associated with stroke. For example, there is a high
prevalence of high blood pressure and, as a consequence, stroke, among afro-caribbean populations.
In the UK, the death rate from stroke has also been
found to be higher among individuals of south asian
origin than among the caucasian population.45
14
What are the consequences of stroke?
As well as accounting for nearly 10% of all deaths,43 56
stroke is a major cause of long-term disability. Worldwide, five million stroke sufferers are left permanently
disabled every year.56 In the UK, over 300,000 stroke
survivors are living with permanent disabilities which
leave them dependent upon others. Stroke can affect
nearly all human functions, making it difficult for many
patients to get out of bed, walk short distances or perform the basic activities of daily living. As well as impairing speech and physical functioning,56 stroke can also
adversely affect mental health.46
Strokes are sudden and they frequently affect people who
were unaware they were at risk. Consequently, they and
their families are often poorly prepared to deal with the
stroke and the damage it brings to their lives.46 Longterm disability can dramatically affect the quality of life of
both patient and relatives.
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Not only does the patient and his or her family frequently
have to shoulder the burden of an unexpected long-term
disability, those living with the aftermath of a stroke are
often in constant fear of death or another stroke.
The consequences of stroke are far from limited to the
elderly. A long-term study assessing outcomes in young
adults (aged 15–45) after a stroke found that within six
years only 49% were still alive, not disabled, had not suffered from a recurrent event or had not undergone major
vascular surgery. The majority of the survivors also reported emotional, social or physical effects that reduced
their quality of life.47
What are the costs of stroke?
Not only are strokes tragic, fatal and debilitating, they
are extremely expensive. It has been estimated that
a single stroke costs the NHS between £9,500 and
£14,000. The factors that cause a stroke have been
found to have a bearing on the severity of a stroke.
For example, people with AF tend to have more severe
strokes which are consequently more expensive.48,62
020
The cost of stroke for the whole
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to be over €38 billion in 2006. This figure included
healthcare costs (about 49% of the total), productivity
loss due to disability and death (23% of the total) and
informal care costs (29% of the total).57 These figures
demonstrate the tremendous financial burden to society
posed by stroke in Europe.
It is clear that stroke is a costly health problem in the UK
and beyond. Stroke accounts for a massive burden on
patients, their carers, families, friends and society. This
burden falls disproportionately on the elderly, who are
most at risk. Early diagnosis and effective management
of atrial fibrillation would help to reduce the burden of
stroke in the UK. Furthermore, the prevention of stroke
with existing, cost-effective therapies in patients at high
risk has the potential to reduce this huge economic burden significantly.50
For example, in patients with AF, who are known to have
a high risk of stroke, the cost of treating a stroke has
been calculated to be almost four times greater than the
cost of prevention with ten years’ anticlotting therapy.97
Strokes cost more than their direct burden on healthcare
budgets. The wider economy suffers from the loss of
productivity associated with disability and death. The
long-term care required for stroke survivors is usually
informal and often overlooked. Yet this also comes with
a tremendous cost to society. Then there is the human
cost, which is incalculable.
Our NHS hospitals are also burdened with providing the
physical space required to treat stroke patients. Stroke
survivors occupy around 20% of all acute hospital beds
and one quarter of all of long-term beds.3
The direct cost of stroke to the NHS has been estimated
to be £2.8 billion every year. This huge sum, however,
does not represent even half of the total costs. The
indirect costs to the wider economy are £1.8 billion and
the costs of informal post-stroke care amount to an estimated £2.4 billion.3
If just the avoidable strokes arising because of AF were
prevented, the NHS would save nearly £60 million in
direct stroke costs alone. In the chart below, the cost
of stroke to the UK can clearly be seen. Both the total
of stroke costs and the cost per head of population are
among the highest spent of any country in Europe.
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Stroke is a massive expense for the NHS and the taxpayer.57
(a)
(b)
Malta
Cyprus
Luxembourg
Estonia
Latvia
Slovenia
Lithuania
Bulgaria
Slovakia
Hungary
Ireland
Romania
Czech Republic
Denmark
Belgium
Portugal
Austria
Finland
Poland
Sweden
Greece
Spain
Netherlands
France
Italy
UK
Germany
Malta
Cyprus
Luxembourg
Estonia
Latvia
Slovenia
Lithuania
Bulgaria
Slovakia
Hungary
Ireland
Romania
Czech Republic
Denmark
Belgium
Portugal
Austria
Finland
Poland
Sweden
Greece
Spain
Netherlands
France
Italy
UK
Germany
0
1000
2000
3000
4000
5000
Total Healthcare
cost in millions
of Euros
Total healthcare
cost
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0
20
40
60
80
Cost per
person
in Euros
Cost
per person
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Chapter 3 - Why does AF matter?
Key points
AF causes half of all dangerous embolic strokes.52
• Strokes in people with AF are more severe and
have worse outcomes than strokes in people
without AF
• AF almost doubles the death rate from stroke
• AF strokes are cardioembolic which leads the
increased risk of more brain damage
• AF increases disability from stroke
• AF increases the risk of a stroke happening
again
The burden of stroke for patients with AF is worse than
just an increase in stroke risk. The strokes suffered by
people with AF are also more severe,72 they are more
frequently fatal4,55 and they are more likely to lead to
disability,4,5,178,72 increased healthcare costs106 and
extended hospital care than strokes in patients without
AF.72 Moreover, AF-related strokes are more likely to
happen again, adding not just to the risk of future
strokes, but also to the potential for increased patient
anxiety and a further reduction in quality of life.
Why does AF lead to more severe
strokes?
The increased severity of strokes in patients with AF is
thought to be related to the large size of the clots that
ultimately block blood vessels in the brain. Almost all
AF-related strokes are cardioembolic; which means that
the clot forms in the chambers of the heart from where
it travels downstream in the blood to the vessels of the
brain. Clots will naturally grow rapidly in size as part of
the body’s safety mechanism to prevent bleeding. The
further a clot travels, the greater opportunity it has to increase in size. Once in the brain, a larger clot can block
larger vessels. The bigger the vessel that is blocked, the
greater the amount of brain tissue that is likely to be
affected. And so it follows that the greater the amount
of brain that has its blood supply cut off, the greater the
chance of a severe stroke, death and disability.
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15%
5%
50%
10%
10%
10%
AF
Ventricular thrombus
Rheumatic heart disease
Acute myocardial infarction
Replacement valves
Other causes
AF nearly doubles the death rate from
stroke
Many aspects of strokes are more severe among AF patients but one of the most dramatic is mortality; the likelihood that a stroke will kill. AF-related strokes kill nearly
twice as frequently as non-AF strokes. In a Danish clinical study, stroke patients with AF were 70% more likely
to be killed than those without AF.72 A larger subsequent
study of Italian stroke patients found that the increase in
death rate among AF patients after 12 months was even
higher; almost double the rate of those without AF.4 An
Austrian stroke registry also demonstrated a near doubling of death rate from stroke in the presence, compared to the absence, of AF (25% versus 14%).55
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12 months after a stroke nearly twice as many AF
patients will have died compared to non-AF
patients55
Year
1
2
3
4
5
6
7
8
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Annual death rate (%)
With AF
Without AF
50
27
14
8
14
6
10
6
11
6
4
3
5
4
4
3
So powerful is this effect, AF has been found to be to be
an independent predictor of death even after adjusting
for age, sex and vascular risk factors.
A trend towards an increase in the overall early death
rate in patients with AF over the last 20 years has also
been reported,51 which may reflect the increasing age
of the population. With both AF prevalence11 and AF
death rate increasing, there is an urgent need to improve
the management of AF, in particular to prevent the most
common fatal consequences, such as stroke.
For a more thorough review of the long-term consequences and costs of AF-related strokes, please see
chapter four.
Patients with AF are therefore a vital target population
for reducing the overall burden of stroke on society.
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Chapter 4 - Cost of AF to individuals
and society?
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Key points
• AF-related stroke impairs stroke survivors’ quality of
life more than non-AF-related stroke
• Permanent disability and other consequences of AFrelated stroke place a heavy burden on carers,
family members and health and social services
• Healthcare costs associated with stroke are higher
for patients with AF than for patients without AF
Significant impact on quality of life
Survivors of strokes have described their subsequent life
as a fate worse than death. This description is not only
dramatic and intuitively apparent, it is also supported
in the scientific literature. For purposes of research, the
impact of a stroke can be evaluated on a scale of zero
to ten where 10/10 represents perfect health and 0/10
represents death.53
In a study that used these scores to evaluate the impact
of stroke on the quality of life for patients with AF, 83% of
patients rated their quality of life after a severe stroke as
equal to, or worse than, death.54
Other scores have been developed to assess specific
aspects of quality of life; such as neurological function.
A comparison of AF and non-AF strokes is presented
in table 4 across several of these aspects. As above,
the scores in the table consistently show that AF-related
stroke has a more negative impact on quality of life than
non-AF-related stroke.72
AF also increases the risk of medical complications following stroke. Compared with those without AF, patients
with AF suffer more frequently from pneumonia, pulmonary oedema (accumulation of fluid in the lungs) and
bleeding in the brain after stroke.55
Heavy burden on carers, families and
society
This sustained impact of strokes has a devastating impact
not only on the individual and their carers but also on
the wider family, particularly children.
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Increased disability and poor health
More than one-third of patients who experience a stroke
return to their home with some level of permanent
disability.56 They then rely on informal care, typically from
family members, to help with their normal daily activities
and to arrange the required additional assistance from
healthcare services.
The disabling consequences of stroke are worse for those
patients who survive an AF-related stroke, than for those
without AF. The presence of AF increases the risk of
remaining disabled after a stroke by almost 50%.5
This disability takes many forms. When compared with
non-AF patients, the presence of AF at the time of stroke
has been found to:
• Increase significantly the loss of ability to perform
normal daily activities,
• Decrease the level of consciousness,
• Increase the partial paralysis of the arm, hand
and/or leg
• Increase the difficulty in swallowing
This was found to be the case both immediately after the
stroke and after rehabilitation.72
Psychological impact on patients, family and
carers
In addition to providing day-today practical care, the
family also has to manage the emotional, mental and
behavioural changes in the patient. These changes can
be among the most difficult for family members to handle. They include mood swings, personality changes,
irritability, anxiety, memory loss and depression.56,58
Faced with such transformations, and the corresponding
effort required to provide vital care, members of the
family can experience a loss of independence, identity
and social life. They also suffer extreme tiredness and
depression. These carers also report fears regarding the
safety of the patient and distress at not having time to
attend to all of the patient’s needs.56,58
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High long-term demand on health and
social services
The rehabilitation and long-term care of stroke survivors
also place a significant demand on formal health and
social services, often involving community nursing, social
care, physiotherapy as well as speech and occupational
therapy.56,59 Research indicates that AF increases the
requirement and costs for the provision of this formal
care compared to non-AF stroke patients.72
Increased hospitalisation, cost and recurrence
with AF-related stroke
AF has been found to be associated with a 20% increase
in the length of hospital stay and a 40% decrease in the
likelihood of patients returning home compared to the
absence of AF in surviving stroke patients.72
As described in Chapter three, almost all AF-related
strokes are cardioembolic; where the clot forms in the
chambers of the heart from where it travels downstream
in the blood to the vessels of the brain. Compelling
research has shown that those who suffer cardioembolic
strokes have a poorer clinical condition on admission to
hospital, experience a longer stay and endure a worse
recovery following discharge than those with non-cardioembolic stroke.106 The same study also found that
costs were higher. The average cost per patient of initial
hospital care for cardioembolic stroke was €4,890 per
patient, compared with €3,550 for non-cardioembolic
stroke, representing an increase of almost 40%.106
In addition to being more severe, cardioembolic strokes
are associated with a higher risk of recurrence than other
types of stroke.60 The increased severity and risk of
recurrence of strokes in patients with AF compared with
other strokes suggests that these patients will
experience a greater impairment in quality of life than
patients without AF.
Case study: a carer’s perspective
“For the past nine months my sister and I have been
acting as full- time carers to our mother, who is bedridden following a stroke. She is unable to do anything for
herself and needs 24-hour care in her own home, where
she feels comfortable and safe. We have had to leave
our husbands and our own homes to give mother our full
support.
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Full-time carers can lose their
sense of
identity
and
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independence as their social life is curtailed. I am also
concerned for my husband’s welfare.”
Case study: a child’s perspective
“The first time I saw Daddy again, he was sitting in a
wheelchair tied on with a sheet so that he would not
fall. His mouth was drooping and he was making funny
noises which we could not understand. I was scared of
him, I didn’t want to see him any more. I was ashamed
of him... he does not remember much about it. He
doesn’t look like Daddy any more.”
High economic cost
As explored in chapter two, strokes are extremely expensive, each one costing the NHS between £9,500 and
£14,000. AF stokes are more severe72 and consequently
can be expected to account for a greater proportion of
the more expensive strokes. This impact of AF becomes
of considerable importance when considering that the
cost of stroke to the UK economy has been estimated
to be £2.4 billion,61 and the cost of stroke to Europe is
likely to be over €38 billion.57
AF-related strokes cost more
In a clinical study that investigated the cost of different
severities of stroke, it was found that the average cost of
a severe stroke was more than three times higher than
the average cost for a mild stroke.48
There is also direct evidence for the increased cost of
stroke in patients with AF. In one study, the average direct
costs of stroke per patient were found to be over a third
higher in patients with AF than in patients without AF.62
The effect of AF on stroke-related inpatient costs was
also recently analysed. The inpatient costs over just a
three-month period were on average 8% higher for each
patient with AF compared to patients without AF.196 As
AF is estimated to be responsible for approximately
between 15-20% of all strokes,63 the increased cost of
AF-related strokes compared with other strokes
represents a significant economic burden.
Direct costs of AF to NHS are huge
All the above studies were focused on the economic
burden of AF associated only with the elevated risk and
severity of strokes. A study from the Office of Health
Economics published in 2009 deliberately set out to
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evaluate the direct costs to the NHS of all AF. The study
investigated the costs of AF alone, as well as the costs of
secondary problems such as AF-related stroke and
AF-related heart failure.
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For 2008, it was calculated that AF accounted for
5.7 million days in hospital beds and a total direct cost
to the NHS of £2.2 billion.61 AF patient days spent in
hospital beds cost the NHS over £1.8 billion. Non-bed
in-patient costs were £124 million and outpatient costs
completed the total at £205 million.
Together with loss of time in employment and contribution to the community of the patient, and most probably
also to those providing informal care, this amounts to
a significant burden on society and on thousands of
individuals.
Strong rationale for stroke prevention
in patients with atrial fibrillation
In conclusion, patients with AF have a higher risk of
stroke and suffer from more severe strokes than patients
without AF. Thus, AF-related stroke imposes an even
greater burden on individuals, carers, families, society
and healthcare resources than stroke in patients without
AF, providing a strong rationale for effective management of AF and prevention of stroke in this high-risk
population.
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Chapter 5 - Who is at risk of AF?
Key points
• For many people AF is silent, with no symptoms to
prompt either concern or medical consultation
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Detection and diagnosis of atrial
fibrillation
Atrial fibrillation is often present without symptoms
Effective AF detection and diagnosis strategies are essential before treatment and the prevention of deadly and
debilitating strokes become possible. Steps to improve
the detection of AF have already been made; guidelines
from the National Institute of Health and clinical Excellence (NICE) recommend that an ECG is required for
all patients with an irregular pulse whether symptomatic
or not.64 ECG stands for electrocardiogram and is the
method doctors use to capture the electrical signature of
heart rhythm problems. However, for this recommendation to be effective, patients first need to have their pulse
checked for irregularity. Modern electric pulse meters
have all but taken over this job from doctors and nurses.
Unfortunately, extremely few modern electrical pulse
check machines are capable of detecting an irregular
rhythm. Consequently, one of the most valuable detection methods for AF has largely been eradicated from the
NHS by the advance of technology.
AF patients, because of their elevated risk both of having
a stroke and having a severe stroke, represent an ideal
focus for stroke prevention. However, we have also discussed in earlier chapters that a substantial proportion of
AF patients are currently undiagnosed or inappropriately
treated. This chapter reviews detection, diagnosis and
decisions on who and how to treat for the prevention of
stroke.
Many patients have other risk factors for stroke, such as
high blood pressure, diabetes and heart disease. For
these conditions they will already be receiving frequent
check ups. The introduction of opportunistic screening
by making routine manual pulse checks during these
check ups would appear to be a prudent, simple and low
cost method to increase the detection of AF and prevent
strokes.
Although AF may be recognized by symptoms such as
palpitations or dizziness it is commonly asymptomatic,
when the patient is unaware of anything that might
indicate that they have AF. This is commonly called silent
AF. Consequently, many people have undetected AF, and
might have had it for some time.8 Studies using heart
monitors that record heart rhythms 24 hours a day have
shown that it is common for a patient to have periods
of both symptomatic and asymptomatic AF.8 It is often
the case that a diagnosis of AF is only made following a
serious complication such as stroke or heart failure.64
Opportunistic pulse checks are a low cost
option
• AF is often not detected until the development of a
serious complication such as stroke or heart failure
• Routine opportunistic pulse checks represent an
effective and cost-effective method of improving the
detection of AF in patients at risk of stroke
• Many methods are used by doctors to determine
stroke risk for an individual patient, and hence the
ideal treatment to prevent stroke
• Patients in the UK may currently be receiving
inconsistent advice and therapy, due to a lack of
consensus on AF risk stratification
22
A UK study, involving almost 15,000 patients, compared
opportunistic screening for AF, as described above, with
another, systematic, method. Compared to routine clinical care, opportunistic screening identified approximately
50% more cases of AF. Systematic screening identified
approximately 70% more case than routine clinical care,
but was associated with a high cost per patient, nearly
five times the cost of the opportunistic approach.139 The
opportunistic screening was associated with a cost of
only £363 per patient. However, only a tiny fraction of
this was for the inclusion of a manual pulse check at
routine appointments. The majority of the cost was ac-
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counted for by the subsequent ECG and interpretation;139
steps already required by the NICE Guidelines upon
detection of an irregular pulse.
The study highlighted the important role of a simple,
routine pulse check, in helping to improve detection of
AF. The policy implications arising from the results of this
study are that an opportunistic approach using pulsetaking followed by ECG is probably the most cost-effective option for any screening programme implemented
through primary care.139
Despite these results, today there is no policy, formal target or recommendation from the Department of Health
that recommends or mandates the routine manual pulse
checks for any group of patients at GP surgeries.
The role of ambulatory monitoring
Episodes of AF can be both short and infrequent which
adds to the difficulty of detection and diagnosis. For
some patients, for example those who have reported
instances of their own pulse being irregular, there is
potential value in the use of heart rhythm monitors that
record the pulse constantly for up to several days at
a time. A patient would need to wear the device for
between 12 and 72 hours but the constant monitoring
would greatly increase the likelihood of a positive diagnosis. When prolonged monitoring is used in ischaemic
stroke patients, AF is detected in one in 20 cases, providing powerful evidence for the routine adoption of such
monitoring in these stroke patients.
Making treatment decisions based
upon risk of stroke
Once an AF patient is identified, it becomes necessary to
make a treatment decision that best addresses the needs
of the patients; lowering risk of stroke as much as possible while not adding further unnecessary risks to the
patient’s health. The treatment options to prevent stroke
will be covered in more detail in the following chapter
but in short; patients at low risk of stroke are often candidates for treatment with the antiplatelet drug aspirin.116
For patients at moderate and high risk of stroke, aspirin
has been shown to offer only modest efficacy despite
having a similar risk for major bleeding as warfarin,65,104
that is therefore recommended for these patients. To
determine who receives which of these two drugs, much
attention has been given to this risk factors for stroke in
AF patients.
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Factors reported to increase www.anticoagulationeurope.org
further the
of stroke
8,66
patients with AF include:
•
•
•
•
•
•
•
Being female
Being elderly
Having previously had a stroke or TIA (mini stroke)
Having high blood pressure
Having heart failure or valvular heart disease
Having diabetes
Having vascular disease
Furthermore, the factors contribute in different ways and
by different amounts to the risks of an AF patient having
a stroke.
For example, a history of stroke or TIA is the strongest
independent predictor of stroke in patients with AF, increasing the risk of another stroke approximately threefold.8 Increasing age also has a marked effect on the risk
of stroke: among patients with AF, the incidence of stroke
is approximately sevenfold higher in patients in their 80s
compared with those in their 40s.67 High blood pressure
increases the risk of stroke approximately threefold in
patients with AF.68 Vascular disease also independently
increases the risk of stroke and death in AF patients.81, 194,197
Specifically, the development of coronary artery disease
in AF patients has been found to be predictive of the
formation of stroke-causing clots.203
Although stroke and AF are both more prevalent in men
than in women,69,70,71 the literature shows that death rate
from stroke is increased fourfold in women with AF compared with twofold in men with AF.105 However, it should
be noted that not all studies have demonstrated such a
significant difference between the genders.105,72
Given that every patient is different, it is necessary for
doctors to work out individual AF patient risk of stroke
from all the above factors. This is called risk stratification.
Many approaches to evaluating individual stroke risk in
AF patients have been developed. Using these, doctors
can quickly assess the patient’s risk and make the necessary treatment decisions.
Approaches to risk stratification
Several different methods are used by UK doctors when
seeking to determine the risk of stroke among AF patients. These all provide risk scores based upon the presence of risk factors including those reviewed above.73,74
Risk calculation schemes vary by the risk factors they
incorporate and in their methods of scoring and risk
evaluation. Schemes in current are, usually known by
their acronyms, include: AFI, SPAF, ACCP, Framingham,
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CHADS2 and CHA2DS2VASc. Furthering potential for
the adoption of different methods among doctors, NICE
developed its own new scheme instead of adopting an
existing option.
NHS Improvement GRASP-AF tool
NHS Improvement has sought to assist GPs with the
adoption of risk stratification among AF patients through
the introduction of the GRASP-AF tool. GRASP-AF is
made available free to all GPs, allowing them to
analyse patient records swiftly and easily for those at risk
of stroke because of AF. The tool automatically calculates
CHA2DS2VASc and CHADS2 scores for all patients, identifying all those in need of anticoagulation. The GRASPAF tool automates multiple steps for GPs, it:
•
•
•
•
•
Identifies AF patients
Searches for risk factors
Calculates CHA2DS2VASc and CHADS2 scores
Searches for current medication status
Searches for reasons for not treating with an
anticoagulant
• Alerts GPs to those patients at risk of stroke but not
receiving anticoagulation medication
Considerable advances could be made in the identification and appropriate treatment of AF patients if GPs
made routine use of this free and powerful tool. More
information on GRASP-AF can be found in the next chapter and at www.improvement.nhs.uk.
The role and limitations of CHADS2
CHADS2 is a simple algorithm that is an evolution of the
AFI and SPAF risk schemes. It is based on clinical trial
results and works on a simple points system:
CHADS2 and how it’s calculated
C
H
A
D
S2
Congestive heart failure:
Hypertension (high blood pressure):
Age greater than 75 years:
Diabetes:
Stroke or TIA:
1 point
1 point
1 point
1 point
2 point
From these risk factors, the acronym CHADS is derived.
The ‘2’ is then added denoting that Stroke and TIA attract double the risk score of the other factors. The points
for a particular patient are then added up allowing doctors to assign the patient to low, moderate or high risk
and prescribe the appropriate treatment.
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of CHADS
other
2
schemes concluded that there were substantial, clinicallyrelevant differences between them. Most were found to
have only a modest ability to predict stroke and that the
proportion of patients assigned to low, moderate and
high risk categories varied widely between the schemes.
For example, while CHADS2 has been found to be a
more accurate predictor of stroke, in patients not on anticoagulation treatment, than the older AFI117 and SPAF118
schemes (from which it was derived), it does not take
account of several common stroke risk factors. Consequently, CHADS2 categorises many patients as at moderate risk despite evidence that many of them would derive
benefit from taking an anticoagulant instead of aspirin.116
The development and validation of
CHA2DS2VASc
Because of these limitations, a further development was
made called CHA2DS2VASc, to complement the CHADS2
scheme. CHA2DS2VASc extends CHADS2 by considering additional common risk factors and focusing on a
continuum of risk as opposed to arbitrary levels of low,
moderate and high risk. The risk factors and scores for
CHA2DS2VASc are listed below.
CHA2DS2VASc and how it’s calculated
C
H
A2
D
S2
V
A
Sc
Congestive heart failure
Hypertension (high blood pressure)
Age greater than 74 years
Diabetes
Stroke or TIA
Vascular disease
Age 65-74
Sex (i.e. female)
1 point
1 point
2 point
1 point
2 point
1 point
1 point
1 point
CHA2DS2VASc was validated in an analysis from the Euro
Heart Survey79 and in several other studies.75 76 77
The most recently published international consensus
guidelines, from the European Society of Cardiology,
have adopted the CHA2DS2VASc scheme and endorses
use of the scheme to categorise the stroke risk among
patients with a CHADS2 score lower than two, to ensure
the most appropriate treatment decision is made.116
Subsequent to the publication of the ESC guidelines,
CHA2DS2VASc has received further support from new
data illustrating that the scheme performs better than
CHADS2 in predicting patients at high risk of stroke.
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The new data also showed that patients categorised as
low risk by CHA2DS2VASc were indeed at truly low risk for
stroke, unlike similarly categorised patient under other
schemes.81
Having different schemes, while confusing, becomes
inevitable as scientific understanding increases and
evidence builds for one method versus another.
For example, at least until the next revision of the NICE
guidelines on the management of AF, many British doctors will be in the challenging position of having different
risk assessment and treatment advice being endorsed by
different authorities. As a result, patients in the UK may
receive inconsistent advice and therapy, depending on
local preferences.
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BLED score has been validated
in large
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80,200,201
groups of AF patients
and has also been recommended in recent Canadian treatment guidelines,198
The new ESC guidelines state that it would seem reasonable to use the HAS-BLED score to assess bleeding risk in
AF patients on the basis that a score of three or greater
indicates ‘high risk’.116 In the light of growing evidence,
the more recent Canadian guidelines recommend that
bleeding risk is assessed using the HAS-BLED score.198
Calculating the risk of treatment-related
bleeding
Despite increasing pressure from advanced stroke risk
calculation schemes and recommendations of new
guidelines, many physicians hesitate to use an anticoagulant because of perceived risks of the patient suffering from dangerous excessive bleeding. This perception
is frequently unjustified. To address this concern with
bleeding risk, the authors of the ESC consensus guidelines included an additional risk calculation scheme for
bleeding among AF patients.
Using data on risk factors for major bleeding from the
Euro Heart Survey as well as from a systematic review of
the literature, a simple bleeding risk scheme, HAS-BLED,
was derived for patients with AF:80
HAS-BLED and how it is calculated
H
A
S
B
L
E
D
Hypertension
Abnormal renal/liver function
Stroke
Bleeding history/predisposition
Labile INR (unstable warfarin impact)
Elderly (eg, >65 years)
Drugs/alcohol
1 point
1 point each
1 point
1 point
1 point
1 point
1 point
for certain drugs plus 1 for alcohol excess – max 2
HAS-BLED aims to provide a simple way to evaluate
risk of bleeding in AF patients so that effective treatment
decisions can be made. HAS-BLED has also been developed to encourage doctors to consider reducing the risk
of bleeding by focusing on correctable risks such as high
blood pressure and poor warfarin control. The HAS-
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Chapter 6 - Treating AF and preventing stroke
Key points
• Direct treatment of AF is frequently necessary to
control distressing and intrusive symptoms; some
heart rhythm treatments also reduce the risk of
stroke
• It is recommended that patients receiving
antiarrhythmic treatment for AF also receive therapy
to reduce the risk of blood clots
In a considerable proportion of patients, control of the
AF itself proves unsuccessful and treatment becomes
entirely targeted at assessing and reducing the risk that a
patient will suffer serious long-term consequences of AF,
particularly stroke and heart failure.
This chapter reviews current treatments both for AF directly and for managing the risk of long term complications independently of the underlying AF.
• Warfarin is safe, effective and cost effective for the
prevention of stroke in the majority of AF patients
Rhythm and clotting
• Warfarin is used less in the UK than recommended
in authoritative guidelines; this under use results
from practical obstacles and, frequently unfounded,
safety concerns
Two treatment approaches underpin the management
of AF. One is to correct the faulty heartbeat,178 and the
other is to manage the risk of stroke by preventing the
formation of clots in the fibrillating heart.
• High blood pressure and diabetes, which commonly
affect patients with AF, also require management to
reduce the risk of stroke
Rate control, rhythm control and cardioversion
Aims of AF management
The immediate aim of AF clinical management concentrates on the relief of symptoms and the assessment of
AF-associated long term risk.116 The greater proportion
of this document is focused on the serious complications
of AF, specifically stroke. For many patients, however, addressing the symptoms of AF represents a much greater
concern than preventing long-term complications. The
symptoms of AF can be debilitating and unpredictable.
Many AF patients report a dramatic fall in quality of life.
As we have learned in previous chapters, many also
suffer from a pronounced decline in mental health. At
diagnosis, it is common for a patient to have endured a
considerable period of time living in fear of symptoms
over which they had no control and of which they had no
understanding. Treatments such as ablation that achieve
the desired symptomatic control by returning the heart
to a normal rhythm also offer the potential benefit of
eliminating the threat of long-term complications such as
heart failure and stroke.
Several strategies are commonly used to treat the heartbeat:
Strategies for treating a faulty heart rhythm
Rate control Slowing an excessively fast pulse with
sustained drug treatment
Rate control is used to treat symptoms
and to relieve stress to the
cardiovascular system
Rhythm
control
Returning the heart to a normal
rhythm with sustained drug treatment
Rhythm control is achieved with
antiarrhythmic drugs that reduce the
fibrillation to control symptoms
Cardioversion
Resetting the heart rhythm suddenly,
usually with an electric current
Ablation
Returning the heart to a normal
rhythm permanently by surgically
blocking chaotic electrical activity in
the atria
For these reasons, it is vital that the drugs and procedures that treat the underlying AF are used in appropriate patients whenever possible.
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Reducing the risk of stroke
Warfarin
Regardless of the course chosen to address the underlying heart rhythm problem, AF patients almost always
need additional management of stroke risk by preventing clots from forming and blocking blood vessels in the
brain.
Warfarin belongs to a class of drugs called vitamin K
antagonists, (VKAs) meaning that they interfere with the
normal action of vitamin K which is involved in the blood
clotting process. Specifically, four proteins that play key
roles in the blood coagulation pathway require vitamin K
for their production. Warfarin inhibits the action of vitamin K, limiting the production of these four anticoagulation proteins.4,17 The anticoagulation pathway is a series
of enzyme-controlled chemical reactions that ultimately
produces fibrin, an insoluble protein that combines with
platelets to form blood clots.
AF disrupts the blood flow through the heart allowing
the formation of a blood clot, or thrombus. Most strokes
are the result of a thromboembolism which is a clot that
travelled to the brain in the bloodstream. Strategies for
the prevention of stroke in patients with AF primarily
involve the use of anticlotting drug therapy. It is recommended that AF patients receiving treatment to correct
their for heart rhythm also receive some form of anticlotting therapy.82
There are three main classes of ‘blood-thinning’ drugs
currently used in the prevention of stroke in patients with
AF
The main types of antithrombotic (‘blood thinning’)
drugs
Anticoagulants Which interrupt the pathway of
chemical reactions that result in the
formation of a blood clot
Warfarin is the recommended oral
anticoagulant (OAC) for stroke
prevention in AF patients
Antiplatelet
drugs
Which limit the aggregation of
platelets; components of the blood
that form a significant part of the
blood clot
Aspirin is the most widely used
antiplatelet agent for the reduction
of stroke risk in AF patients
Thrombolytics
The AF Report
Which break up blood clots once
they are formed. Thrombolytics are
generally reserved for use in the
acute setting and do not play a
role in long-term stroke prevention
www.anticoagulationeurope.org
A narrow effective range and a need for
monitoring
Despite this useful anticoagulant activity, warfarin has
only a narrow range of concentration in the blood in
which it is both safe and effective. Maintaining warfarin
within this range is also complicated by interactions with
food and other drugs18 that can significantly alter blood
levels of warfarin regardless of the dose taken.
If the level of warfarin is too low then the patient is not
benefiting from a reduced risk of stroke. If the level is too
high, the anticoagulation properties put the patient as an
increased risk of bleeding.
Thus, the management of patients on warfarin can be
challenging, and frequent monitoring is required so that
the dose can be adjusted to maintain effective and safe
therapy. For monitoring, a measure of clotting time is
taken (called the pro-thrombin time). If clotting takes
too long then the dose needs to be reduced. If clotting
happens too quickly, the dose of warfarin needs to be
increased.
Understanding clotting time and INR
So that all pro-thrombin tests can be compared accurately with one another, the result of the test is converted
to a ratio between the test result and a standard prothrombin time. This ratio is called the international normalised ratio (INR). Consequently, it is the INR that a
physician and patient will try to keep within a target
range to ensure warfarin remains at ideal levels in the
blood. A target INR of 2.0 - 3.0 is typically recommended for patients receiving warfarin.8,83 If the INR is too
high, a patient is at increased risk of bleeding; too low,
and the risk of a blood clot becomes high.
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Drawbacks of warfarin are not insignificant and include
unpredictable interactions with food which often necessitate significant lifestyle changes. One of the many drugs
with which warfarin interacts is amiodarone, an anti-arrhythmic drug used in the treatment of AF.84 The inconvenience of INR monitoring and frequent dose adjustment also represents a burden for many patients.
Efficacy of warfarin in clinical trials
Warfarin has been shown to be very effective at reducing
stroke in AF patients. Systematic reviews of clinical trials
in patients with AF have shown, compared with no
therapy, that warfarin can provide a 62-68% reduction
in stroke and a 26-33% reduction in the death rate85,87,88
without significantly increasing the risk of major bleeding. This means that for every 1,000 patients treated with
warfarin, 31 strokes will be prevented each year.85 Given
the cost and harrowing consequences of stroke, this is an
equations that strongly favours the use of warfarin.
Importantly for patients with AF, it has been shown that,
when the dose is monitored and adjusted, warfarin is
effective in preventing both mild and severe strokes.89,90
Warfarin in clinical practice
The practical difficulties in maintaining the target INR,
understandably raise concerns that the efficacy and
safety observed with warfarin in clinical trials might not
reflect what can be achieved in routine clinical practice.91
Clinical trials monitor patients very closely, more than
might be practical or possible in routine clinical practice.
Also, to meet trial design and ethical requirements,
clinical trials often exclude patients at high risk of
bleeding while also recruiting relatively few elderly
patients.85,91
These concerns were largely refuted by observational
studies that reviewed the history of large groups of
patients cared for in routine clinical practice. In a largescale study of more than 11,500 AF patients, warfarin
provided a 39-60% reduction in the risk of thrombolembolic events (stroke and peripheral embolism) and a
31% reduction in the risk of death compared with either
patients taking therapy or patients only taking aspirin.92
The risk of an intracranial bleed was almost doubled with
warfarin, but still remained low with no significant association between warfarin and non-intracranial bleeding.
The authors concluded that the results of clinical trials of
warfarin translate well into clinical care for patients with
atrial fibrillation.92
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Further investigations in the clinical
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Italy and the UK have demonstrated reductions in the risk
of stroke of between 26-66% in patients with AF receiving
warfarin compared with those not receiving warfarin.93,95
Despite an increased risk of bleeding, the overall rates of
ill health and death were significantly lower in the Italian
patients receiving warfarin than in those not receiving
warfarin.94,95 However, the risk reduction observed in the
UK study (26%) was substantially lower than in clinical
trials.94 Further analysis has highlighted management
differences between anticoagulation clinic care and
routine medical care, with patients in routine clinical care
spending less time within the target INR range.94,150
While the efficacy and safety profiles of warfarin do
appear to be somewhat less favourable in routine
medical practice than in clinical trials, the benefits
outweigh the risks in the majority of patients.
Improving warfarin use with GRASP-AF
Warfarin is currently recommended in UK and European
guidelines as first-line therapy in patients with AF and a
moderate or high risk of developing stroke.8,83 Despite
evidence that following the guidelines results in improved
patient outcomes,106 there is significant under-use of warfarin illustrating that the guidelines are not always
followed. Thus, many patients with AF and a moderateto- high risk of stroke do not receive anticoagulant
therapy and therefore remain at high risk for stroke.112,19
As introduced in the previous chapter, GRASP-AF is a
tool for GPs that automates the identification of patients
for whom warfarin treatment should be started. GRASPAF data, collected from use in over 1,500 English GP
practices, supports the NICE statistics that only around
half (55%) of those with AF at high risk are prescribed
warfarin.
GRASP-AF is part of a broad NHS Improvement programme to raise awareness of AF and stroke risk, thereby
reducing the number of AF-related strokes. An important
element of this work is improving the management of
stroke risk in patients with AF by promoting appropriate risk assessment, and the prescribing of appropriate
anticoagulation. This is achieved through the use of the
GRASP-AF tool that is free for GPs to download from the
NHS Improvement web site. The GRASP-AF tool identifies
patients with AF, calculates their stroke risk, and also details their current management. This information is simply
summarised, allowing GPs easily to audit their current
management of AF against best practice guidelines.
The AF Report
www.afa.org.uk
There is also a facility to upload the data to CHART,
a web-based comparative analysis tool. This enables
anonymous comparison of data with other practices.
Local and regional analyses are also made possible by
comparisons between Primary Care Trusts, Cardiac and
Stroke Networks and Strategic Health Authorities. To
date, 1,500 GP practices in England have run GRASP
and uploaded their data to CHART – this growing database is probably the largest AF database in the world.
Illustrating the potential of warfarin to reduce stroke risk,
GRASP-AF is already leading to improvements in anticoagulation and management of AF in general practice.
Cost of warfarin in stroke prevention in atrial
fibrillation
In a UK study, the cost of preventing one AF-related
stroke per year using warfarin was estimated to be
£5,260.96 This cost of prevention appears to be
favourable when compared with a European average
cost of £11,799 for treating a stroke.62 In another study
of patients with AF in the UK, the cost of treatment of a
stroke over a 10-year period was estimated to be almost
four times greater than the estimated 10-year direct costs
of anticoagulation,97 further indicating that prevention is
a cost effective option, regardless of the costs associated
with warfarin and its challenges. Numerous other studies
have provided additional evidence that anticoagulation
with warfarin is cost-effective in patients with AF at a
moderate or high risk of stroke when compared with no
therapy or aspirin.105,99
As well as efficacy and safety, modern health providers
also have to take into account the cost-effectiveness of a
treatment. This can be challenging as it necessarily puts
a price on human health and life. However, done
carefully, cost-effectiveness comparisons allow many
different treatments to be assessed on a level playing
field. In the absence of unlimited funding,
cost-effectiveness comparisons allow the NHS to make
treatment decisions that will have the greatest benefit for
the most people.
To make these comparisons, health economists use the
QALY; a quality-adjusted life-year. To illustrate, a year in
perfect health is equal to a QALY of one. A year in less
than perfect health would have a QALY less then one.
The worse the health, the closer the QALY becomes
to zero.
The AF Report
Treatment of AF patients withwww.anticoagulationeurope.org
warfarin020
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found
to be cost effective, i.e., associated with a low cost per
QALY, particularly in patients considered to be at
moderate-to-high risk of stroke.99 In one study, the cost
of warfarin for AF patients with one additional stroke risk
factor was reported to be $8,000 per QALY saved109
well below the threshold of acceptable cost effectiveness
of £20,000 - 30,000 per QALY established by NICE in
the UK.100
It should be noted that the cost effectiveness of warfarin
is dependent on achieving a significant reduction in the
risk of stroke. Practical difficulties in maintaining target
INR values may result in warfarin being less cost effective
in clinical practice than in clinical trials. INR monitoring
in clinical practice may also incur additional costs, to the
patient, carer and society, not captured in the
cost-effectiveness studies.
Thus, it is important that stroke prevention in clinical
practice is improved so that it is as cost effective as in
clinical trials. This might be achieved through new
strategies that deliver optimal management with
warfarin. It might also be achieved following
technological advances, or new treatments that
overcome the current challenges of warfarin.
Aspirin
One of many actions of aspirin is to reduce the activity of
platelets during clotting. Limited platelet aggregation
reduces the risk of a clot from forming which, in turn,
helps to prevent a stroke.101
In patients with AF, aspirin reduces the risk of all strokes
by approximately 22% compared with placebo. For
severe, disabling strokes, the reduction in risk with aspirin
compared to placebo is smaller (13%).86 Clinical trials
directly comparing aspirin with warfarin in the prevention
of stroke in AF have shown warfarin to be significantly
superior, reducing the risk of a stroke by approximately
half compared with aspirin.107,129 Despite perceptions
that it may be safer than warfarin, a major drawback of
aspirin is that it increases the risk of bleeding, particularly
in the gastrointestinal tract.65,104
Aspirin is therefore recommended only in patients with a
low risk of stroke and in those who cannot take warfarin.8, 83
It should be noted, however, that there is doubt as to the
benefit of aspirin in patients at low risk of stroke.108, 98
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Managing other conditions that
increase stroke risk
AF commonly co-exists with other conditions, such as
high blood pressure and diabetes, which themselves can
contribute to the risk of blood clots and stroke. The risk
in patients with several of these conditions is cumulative
that is, the more conditions that predispose to stroke,
the greater the risk. Even in patients who are receiving
antiarrhythmic and anticlotting therapy, effective
management of these other conditions can further
reduce the risk of stroke.
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In the medium-to-long term,www.anticoagulationeurope.org
alternative
that
combine convenience with a efficacy and safety could
help to improve further the prevention of stroke in
patients with AF. The development of such treatment
promise considerable improvements in the management
of patients with AF. Several clinical studies of potential
new treatment are ongoing and early indications are
positive. New and emerging treatments and recentlypublished clinical trial results are discussed in more detail
in the chapter “New developments for stroke prevention
in patients with atrial fibrillation”.
Blood pressure control is particularly important in the
management of AF, as uncontrolled blood pressure
increases the risk of stroke three-fold.68,110
AF in patients with diabetes is also associated with a very
high risk of stroke. One study in patients with diabetes
found that those who also had AF had a more than
60% greater risk of death from all causes than patients
without AF; they also had an increased risk of death from
stroke and heart failure.111
It is therefore clear that conditions which increase the
risk of stroke and that co-exist with AF must be carefully
managed.
The outlook for stroke prevention in
patients with atrial fibrillation
To summarise, patients with AF should be managed
holistically and treated with drugs or other strategies that
control the abnormal heart rhythm itself, as well as with
anticlotting therapy to reduce the risk of blood clots and,
hence, stroke. Warfarin has been shown to reduce the
risk of stroke in patients with AF in both clinical trials and
clinical practice. Importantly, warfarin has proven efficacy
in reducing the risk of severe, fatal or disabling strokes.
In addition, anticoagulation with warfarin has been
demonstrated to be cost-effective in patients with AF and
a moderate-to-high risk of stroke. Warfarin is, however,
associated with major, well-recognised drawbacks.
Nevertheless, it remains frontline therapy in this
indication. Thus, in the immediate term, improved
detection of asymptomatic AF and increased use and
optimisation of warfarin therapy is important to reduce
the incidence of severe strokes in patients with AF.
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Chapter 7 - The importance of guidelines
Key points
• Patients at moderate and high risk of stroke should
receive anticoagulation therapy such as warfarin
• Aspirin is currently recommended only for patients
at a low risk of stroke
• Robust evidence for the effectiveness of aspirin in
AF patients is limited
• Aspirin is associated with major bleeding risks
• While two sets of guidelines are directly applicable
to the UK, neither benefits from widespread
adherence
• In the UK fewer than 55% of at-risk patients receive
adequate, guideline-adherent therapy to prevent
blood clots
• The drawbacks of current therapies, a lack of
physician and patient education, and poor
motivation of GPs to change practice, may
contribute to this problem
Summary of guidelines
Data show that under-use of anticoagulant therapy in AF
patients at a high risk of stroke is associated with a significantly greater rate of thromboembolism, while overtreatment is not associated with a significantly higher risk
of bleeding.112 Given this evidence, and that reviewed
in the previous chapter, the importance of clinical guidelines which advocate the use of warfarin in patients at
moderate and high risk for stroke cannot be overstated.
Different recommendations in NICE 2006 and
ESC 2010 guidelines
Several sets of guidelines exist for the treatment of AF
and the prevention of stroke. In the UK, however, there
are two guidelines that have direct relevance: those published by the National Institute for Health and Clinical
Excellence (NICE) in 2006 and those published by the
European Society of Cardiology (ESC) in 2010.
The AF Report
The ESC 2010 guidelines have replaced many earlier
international publications, including those cited by NICE
in its 2006 guidelines.113 However, clinical guidance
from NICE has a special status in the UK; as the formal
guidance that all health professional are expected to
take into account when making treatment decisions.114
It is important to note that the NICE guidelines reflect the
start of the art in 2005. However, until and unless NICE
updates its guidance to accommodate the more recent
ESC 2010 publication, healthcare professionals in
England and Wales will remain in the challenging
situation of having to decide between two, occasionally
conflicting, guidelines.
The clinical guidelines from NICE are based on systematic reviews and cost-effectiveness analysis.32 This differs
from the methodology of expert consensus that was used
to produce the ESC 2010 guidelines, as well as most
others.115
The guidelines differ in the specific treatment recommendations that they make regarding stroke prevention in
patients with AF. Until the publication of the ESC 2010
guidelines, there was a general agreement between
international expert consensus guidelines that patients at
low risk of stroke should receive aspirin therapy, those at
moderate risk should receive aspirin or oral anticoagulant therapy (eg, warfarin) and those at high risk should
only receive therapy with warfarin. This raises therapeutic uncertainty for the doctor when faced with moderate
risk patients; should aspirin or warfarin be given? Stroke
risk classification schemes that assign a high proportion
of patients to moderate risk compound this therapeutic
uncertainty and are less helpful.
New guidance that all ‘low’ and ‘moderate’ risk
patients should be on warfarin
In contrast, the ESC 2010 guidelines recommend a risk
factor approach and a reduction in emphasis on the
artificial categories of low, moderate and high, which
have been found to be poor predictors of stroke risk.
The ESC guidelines recommend that those at genuinely
low risk (with a CHA2DS2VASc score of zero) should
receive no antithrombotic therapy or, in some cases,
aspirin. For those with risk factors for stroke (ie, with a
CHA2DS2VASc score of one or higher) most should
receive oral anticoagulation therapy.116
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Treatment implications of not using ESC 2010 guidelines
Risk of stroke
Low
Moderate
High
NICE 2006 Guidelines
Aspirin
Aspirin or Warfarin
Warfarin
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ESC 2010 Guidelines
No antithrombotic therapy (or *aspirin)
Warfarin (or *aspirin)
Warfarin
* indicates the guidelines’ preferred choice
The ESC 2010 guidelines draw upon CHA2DS2VASc, a
new method of risk stratification that was introduced in
chapter five. CHA2DS2VASc is an evolution of the stroke
risk scheme developed by NICE for its 2006 guidance
and is more inclusive of common stroke risk factors.
One recent analysis of patient registry data (registry data
can provide insights into outcomes within routine clinical
practice) found that the benefits of oral anticoagulation
therapy outweigh bleeding risks in all but those patients
at genuinely low risk, ie, those with a CHA2DS2VASc
score of zero.202
CHADS2 has been found to be easy to use, but still a
modest predictor of stroke; similar to earlier schemes, in
patients not on anticoagulation treatment.117,118 CHADS2
does not take account of several common stroke risk
factors, categorising many patients at moderate risk despite evidence than many of them would gain significant
benefit from taking an anticoagulant instead of aspirin.116
Until the 2006 NICE AF guidelines are updated to reflect this advance in understanding of stroke risk, many
patients will continue to receive aspirin when they could
derive a significantly increased reduction in stroke risk,
with no additional risk of major bleeding, if they were to
take warfarin instead.
Guidelines: theory versus practice
Regardless of the difference between these two authoritive guidelines, neither is uniformly followed and warfarin
treatment remains underused in the UK. Even NICE’s
own data shows that of all those with AF who should be
on warfarin, almost half are not.119
This is not just a UK problem; in a study conducted in
seven European countries, it was found that only 8.4% of
patients with AF who had a stroke were receiving anticoagulants at the time of their stroke, and the proportion decreased by 4% per year with increasing age.5 A
review of the scientific literature from 2000 indicated that
only 15–44% of eligible patients with AF were receiving
warfarin.23
32
Yet, when asked, physicians demonstrate both awareness
of the guidelines and agreement with them. For example, a questionnaire was used to examine the adherence of Swedish physicians to European and national
guidelines.19 Of 498 physicians who responded, more
than 94% stated that patients at risk of blood clots with
chronic AF should receive long-term anticoagulation
therapy. The investigators also evaluated the records of
200 patients hospitalised for AF to check whether or not
treatment matched the answers to the questionnaire. In
total, 108 patients had chronic AF with one or more risk
factor for stroke, and no other reason not to take to warfarin, but only 40% of these patients received warfarin.19
This study further highlights the discrepancy that is often
found between guidelines and what happens in clinical
practice.
Another study documented the medications being taken
by AF patients when they suffered an ischaemic stroke.
It found that only 10% of these patients had been taking
an effective dose of an anticoagulant. Nearly a third
were on no antithrombotic treatment at all (29%). A
further 29% were on aspirin and another 29% were on a
non-therapeutic dose of warfarin.
Not all studies into the use of warfarin in AF patients
provide evidence of under-use.121,143 According to recent
surveys in different parts of Europe, the proportion of
patients with AF at high risk of stroke who are receiving
adequate anticoagulation is most commonly around 54–
61%,122,112 but this figure is as high as 88% in settings
where guidelines are being more successfully applied in
the real world.123,124
Reasons for poor adherence to
guidelines
Adherence to guidelines for the prevention of stroke in
patients with AF may be low for several reasons. These
include difficulties in maintaining INR within the therapeutic range18 and physicians’ concerns about bleeding
risk, particularly in the elderly.125 This section reviews
some of these challenges, and also examines the way in
which the Department of Health rewards GPs for reaching targets, and how that might contribute to poor adherence to guidelines in the UK.
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The motivation of general practitioners
When the payment of UK general practitioners was
reviewed in 2004, a new scheme was introduced called
the Quality Outcomes Framework (QOF).126 QOF was
designed to reward GPs for the quality of the care that
they provided, instead of for how many patients they
treated. The scheme also provided additional resources
that could help GPs implement new services to address
local needs. Currently, GPs can work to secure up to
1,000 QOF points by meeting predetermined
performance targets in four broad areas: Clinical,
Organisational, Patient Experience and Additional
Services. A total haul of 1,000 points represents an
additional payment to GPs of over £13,000.
Specifically for AF, within the current QOF scheme, up to
12 points are available for GPs achieving a high percentage of…
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• In those patients with Atrial
Fibrillation
in whom
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there is a record of a CHADS2 score of less than
one, the percentage of patients who are receiving
anticoagulants
Both of these proposals are to be welcomed by those
seeking better adherence to clinical guidelines and more
effective treatment of UK patients at risk of stroke because of AF. Moreover, the second of the two proposed
new indicators specifically addresses the failing of the
current QOF indicator to provide GPs with motivation to
prescribe anticoagulation therapy.
The proposed QOF reward for prescribing an anticoagulant in patients at moderate or high risk appears
reflective of the ESC 2010 guidelines and perhaps
demonstrates that UK policy makers are keen to accommodate the recommendations of the new ESC guidelines
even before there is opportunity to accommodate them
in revised NICE guidelines.
‘… patients with atrial fibrillation who are currently
treated with anticoagulation drug therapy or antiplatelet
therapy.’126
Difficulties of keeping warfarin within the therapeutic range
It is reasonable to expect that many patients diagnosed
with AF will already be taking aspirin for another condition. It is also relatively simple to start and manage a
patient on aspirin (antiplatelet therapy) compared to warfarin (anticoagulation therapy). Consequently, the way
the target is written enables GPs to receive the maximum
QOF reward just by having AF patients on aspirin, even
if none of them is on warfarin.
Many patients find the frequent monitoring and necessary
dose adjustments associated with warfarin inconvenient
and time consuming, and may miss appointments. Research has shown that AF patients in routine clinical care
were able to maintain a target INR for over half the time
(56%). Of the considerable remaining time, patients
were above the target range for 30%, and below the
target range for 14%.143
Consequently, QOF today provides virtually no motivation for GPs to put patients on warfarin in accordance
with the NICE 2006 or the ESC 2010 guidelines.
The QOF target described above is, within the scheme,
called an indicator. In March of 2011, NICE opened
a consultation on proposed revisions to the QOF indicators for AF. Encouragingly, the proposed revisions
represent the possibility that GPs might become more
effectively motivated to adhere to guidelines.128 Specifically, two new indicators were submitted for consultation.
If these new indicators are adopted, GPs will receive
QOF rewards dependent upon:
This has unsettling implications. If around half of all
patients in need of anticoagulation aren’t prescribed
warfarin119 and if those who are have either ineffective
or unsafe blood levels of warfarin for nearly half of the
time,143 then perhaps only a quarter of patients at any
one time is receiving the therapy they need to safely
lower their risk of stroke.
• The percentage of patients with Atrial Fibrillation
in whom stroke risk has been assessed using the
CHADS2 risk stratification scoring system in the
previous 15 months
The AF Report
This becomes ever more worrisome when remembering
experts’ estimates that only about half of all AF patients
are actually diagnosed. The vast majority of these undiagnosed patients would be expected to be at moderate
or high risk of stroke,127 and, hence, in need of warfarin
therapy according to the ESC 2010 guidelines. As illustrated in the table below, perhaps only a fifth of patients
in need of warfarin to reduce risk of stroke actually
receiving safe and effective anticoagulation treatment at
any time.
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Very few warfarin patients receive effective and safe
treatment
Percentage
Of every 100
AF patients
c.60%
60
97%127
58
Number
anticoagulated
54%119
31
Number in
INR range
56%143
18
AF patients
diagnosed
AF patients
at moderate
or high risk
Even if the estimated for the number diagnosed is incorrect and, for example, only 30% of AF patients are
undiagnosed, the estimate for the number of patients
receiving safe and effective anticoagulation would rise
only to 21%.
When patients do not receive close monitoring, which
is not usually available in routine clinical practice, they
have been found to be outside the target INR range
for longer than when strict monitoring is imposed upon
them.142 Clearly patients are facing challenges with
their therapy when not under close supervision, and are
therefore put at increased risk of a potentially-dangerous
blood clot or of uncontrolled bleeding.
Physician concerns about bleeding risk
Many physicians resist the use of warfarin in the elderly,
largely on grounds of safety. The evidence, however,
strongly favours the use of warfarin in older patients. The
incidence of stroke among patients aged 75 years or
more with AF is lower in those who are receiving warfarin than in those taking aspirin, without increasing the
risk of haemorrhage.129
Despite this, research has demonstrated repeatedly
that many physicians over-estimate the risk of bleeding
associated with the use of warfarin and under-estimate
its benefits in preventing thromboembolism and stroke;
conversely, they have been shown to under-estimate
the bleeding risk of aspirin therapy and over-estimate
its benefits.20,125,21 As a result, eligible patients are not
receiving therapy that could prevent strokes.16 For many
physicians, bleeding risk is a particular concern in the
elderly, who are more prone to falls, more likely to have
suffered previous major bleeds and who are subject to
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many additional problematicwww.anticoagulationeurope.org
factors 020
associated
with old
132,134
age.
However, evidence has shown that none of
these factors, not previous bleeds, falls or old age itself
has any impact on increased risk of bleeding associated
with warfarin.
While the bleeding risk with warfarin is no worse than
that with aspirin, especially in the elderly, physician
experience of major bleeding events associated with
warfarin can profoundly reduce prescription of warfarin.135 A study investigated the behaviour of physicians
treating AF patients who had bleeds while on warfarin.
Patients treated in the 90 days after the physician had
encountered a bleeding event were significantly less
likely to receive a prescription for warfarin than patients
treated before the bleed.135 In contrast, having a patient
who experienced a stroke while not receiving warfarin
did not influence prescribing behaviour with subsequent
patients.135
In other words, a bleeding event may make a physician
less likely to prescribe an anticoagulant but a stroke does
not increase the likelihood that a physician will prescribe
and anticoagulant.
Two theories have been put forward to explain this phenomenon. The first is based upon a theory that when we
predict the probability of an event, we are influenced by
the ease with which those events can be remembered.
Since a major bleed is likely to be memorable, this
might create a perception among physicians that bleeds
are more likely than is actually the case.136 A second
theory suggests that when making choices, we tend to
select the one we will least regret.137 It is arguable that
a decision to add to bleeding risk by making a change
(prescribing warfarin) is less appealing than a decision
to add to stroke risk by doing nothing. This may also be
in keeping with a principle of the Hippocratic oath, to
‘do no harm’.135 While of interest, there is no evidence
that an understanding of these two possible influences
on prescribing behaviour has any impact on the number
patients who remain at high risk of stroke despite strong
evidence that warfarin would reduce that risk without a
prohibitive risk in bleeding.
Discrepancies between patients’ and physicians’
perceptions of stroke and bleeding risk
Much of proposed future NHS policy is founded on a
desire to engage patients in the path of treatment recommended to them, giving them both choice and control.
This is neatly captured in the line, ‘no decision about me,
without me’.
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A study that compared patients’ and physicians’ perceptions of risk illustrates how such a shift toward patientcentred care might influence the prevention of stroke in
AF patients.
A group of physicians, and another of patients at high
risk of stroke, were asked the same set of questions
about when anticoagulation therapy was justified according to the reduction in stroke risk. Following in-depth
explanation of the bleeding risks involved, 74% of the
patients were willing to take warfarin if prevented just
one stroke in 100 patients over two years. Yet, when
confronted with the same question, only 38% of physicians were willing to prescribe warfarin for the same
risk reduction.138 This result suggests that if patients
were sufficiently informed about, and then involved in,
treatment decisions, many more of them would receive
stroke-preventing anticoagulation therapy than if just left
to the doctors.
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To summarise, adherence towww.anticoagulationeurope.org
guidelines
the 6875
prevention
of stroke in patients with AF is often poor. The reasons
for this appear to be related primarily to the drawbacks
associated with warfarin therapy and to a lack of physician and patient education regarding the benefit-to-risk
ratio of therapy. There is also a clear need for a change
in the way that UK GPs are rewarded for treating AF
patients. The current system fails to provide motivation
to follow guidelines. The proposed change to this system
is to be welcomed, as is the indication that UK policy
makers appear to endorse elements of the most recent
international guidelines from the ESC.
The same study also asked questions about the number
of bleeds that were acceptable with warfarin and aspirin,
having first explained the stroke risk reduction with which
each treatment is associated. Of the physicians,
46% were willing to accept more than ten bleeds in
100 patients treated with warfarin over two years. In stark
contrast, the patients were much more willing accept
bleeds on warfarin given the stroke risk reduction possible. Of the patients, 85% were willing to accept more
than ten bleeds in 100 patients over two years.
The study also suggested that physicians perceive the risk
of bleeding to be higher with warfarin than with aspirin,
perception that we know is not supported by the clinical
evidence.129
These results indicate that patients place more value
than physicians do on the avoidance of stroke, and less
value on the avoidance of bleeding.138 For the effective
prevention of strokes, it appears important that the views
of the individual patient are taken into account when assessing whether to use anticoagulant therapy.
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Chapter 8 - Current challenges
Key points
If the prevention of a silent epidemic of AF-related
stroke is to be prevented, it is vital that we address the
following barriers to reduced stroke risk:
• Insufficient detection and diagnosis strategies
• Low patient awareness and understanding
• Limitations of current treatments
• Incomplete knowledge among healthcare
professionals
• Inequity of patient access to effective management
• Insufficient communication to ensure a continuum of
care for patients
• Guideline differences and low guideline adherence
As has been discussed at length in this report, there are
many and varied obstacles to the effective prevention of
stroke in AF patients. This chapter identifies and summarises seven major challenges to effective stroke prevention among AF patients, as captured above in the key
points.
Insufficient detection and diagnosis
Without effective detection and diagnosis of AF between
a third and a half of patients affected will only be identified once it is too late; having suffered a potentially
debilitating or lethal stroke. If a lack of detection and diagnosis continues, then many patients will be denied the
opportunity to benefit from treatments that can dramatically reduce their risk of stroke.
Strategies are urgently needed to improve detection and
diagnosis of AF. Existing research suggests that routine
pulse screening has a role to play,139 as does public
education on the need to investigate an irregular pulse.
Any solution will need to involve promoting pulse checks
among the general public, and the importance of having
an irregular pulse investigated. The role and value of
screening programmes will need serious review, especially following the positive results of the SAFE study.139
Many pieces are already in place; NICE already recommends that all patients with an irregular pulse receive an
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ECG to make a diagnosis and the SAFE study uncovered
the marginal additional costs of taking a manual pulse.
The SAFE study also found that GP and practice nurse
performance in interpreting ECGs was not encouraging,139
identifying another potential challenge to the effective
diagnosis of AF in primary care.
Low patient awareness and understanding
Wider access to information
Many patients have poor understanding of AF and of the
treatments they take because of it. We know from one
study that 37% of documented chronic AF patients were
unaware that they had AF and nearly half didn’t know
why they were taking warfarin. A similar number didn’t
know they were at risk of clots that could cause stroke.
Sixty percent felt that their underlying condition (AF) was
not severe.140
These findings are backed up be other sources including
surveys of patients from patient advocacy organisations
and from qualitative research among patients.
An extensive international survey conducted by the
patient organisation, AntiCoagulation Europe (ACE),
revealed that a quarter of the surveyed patients did not
remember receiving any information on AF at diagnosis,
and over one-third felt that their doctor could have told
them more regarding their medication and how it would
affect their lives. Particular lack of awareness among patients was noted with regard to the potential interactions
of warfarin with common over-the-counter medicines
and herbal remedies.141
From a qualitative study of AF patients’ experiences it
is clear that the above findings should not have been
surprising. The study reported common and disturbing patient experiences during particular phases of the
pathway of care. All patients involved in the research had
AF which was both recurrent and symptomatic. Before
being diagnosed, patients reported confusion and fear
of symptoms, and were often puzzled during a search to
understand what they meant. Patients reported that fre-
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www.afa.org.uk
quently no explanation of symptoms was given by healthcare professionals, and that symptoms were dismissed as
‘panic attacks’.
At diagnosis, patients reported relief, hope for the future
and validation of their search for understanding of the
symptoms. However, the time of diagnosis was also associated with many less positive experiences with healthcare professionals:
• Lack of information and support from healthcare
professionals
• No education of the course of AF, or information on
what to expect in the future
• No acknowledgement of the negative impact that
symptoms were having on patients’ lives
• Inadequate education on how to manage symptoms
Following the initiation of management, a new range of
negative patient experiences were reported. The unpredictable recurrence of symptoms was associated with
distress, anxiety and a loss of control. Recurrent symptoms were commonly associated with a perception of
treatment failure and accompanied by a fear of suffering
a debilitating stroke.
So not only are patients are not receiving or retaining
information during consultations with their doctors, there
is also evidence that AF patients feel abandoned, dismissed, without support and without understanding at the
hands of the healthcare professionals charged with the
care of their AF.28
Better adherence to therapy
According to AntiCoagulation Europe, adherence to
therapy is strongly dependent upon patients’ understanding of their condition. Without the proper information
or guidance, adherence can be poor, leaving patients
at risk of bleeding or stroke. This report is supported by
data showing that adherence to warfarin therapy increases when patients are supervised and have easy access to
professional support.142
We know that AF patients in routine clinical care were
able to maintain a target INR for over half the time
(56%). Of the considerable remaining time, patients were
above the target range for 30%, and below the target
range for 14%.143
Insights into these research findings were uncovered by
the ACE patients survey. It was found that, while nearly
three-quarters of patients knew their target INR, over a
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third believed that being outside
the target
range
had no
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major effect on their health. Only 30% of patients had
been in their target INR range in all of their last 5–10
monitoring sessions, and 7% had not been in their target
INR range in any of their last 5–10 sessions.141
Greater patient empowerment
Patient empowerment is associated with improved clinical outcomes,144 and has been made central to the current focus of the NHS. For a patient to be empowered,
it is necessary that he or she has sufficient knowledge to
be actively engaged in treatment decisions, in the setting
of treatment goals and in evaluating the outcomes. Specific to the stroke prevention efforts required in AF, patient
education and involvement in the management of warfarin therapy have been shown to reduce the risk of major
bleeding.145 Patients cannot become empowered without
access to information which needs to be accurate, consistent and easy to understand. Limits on the accessibility
should also be removed wherever possible by addressing
different levels of literacy, by not relying on a single format (e.g., print or internet) and by making the information
available in appropriate languages.
Barriers to patient empowerment extend far beyond the
accessibility of information; they include factors such as
time pressure on healthcare professionals, their misperceptions of patient needs and poor continuity of care
between healthcare professionals.
Limitations of current treatments
The limitations of current treatments represent a significant challenge to the effective reduction of stroke risk
in AF patients. Among the group of patients who are
diagnosed, and who would benefit from warfarin, nearly
half don’t receive it.119 And that those taking warfarin,
are only benefiting from reduced stroke risk, with no increase in bleeding risk, for about half the time.143 As we
have see in earlier sections, there are many drawbacks
with warfarin and almost all of these can be traced back
to the narrow therapeutic range and the ease with which
lifestyle choices, foods and other drugs can push blood
levels outside of that range.
There is clearly a need for new therapies that treat AF,
prevent blood clots and prevent AF-stroke without the inconvenience and disadvantages of warfarin and aspirin.
Understandably, AF patients currently taking anticlotting
therapy are all to aware of this need. When surveyed,
68% of chronic AF patients expressed their interest in
new anticoagulation drugs for which routine monitoring
was not needed.151
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Progress in this area of new therapies is discussed in
more detail in the earlier section but new anticoagulant
drugs are in development. Available clinical data suggests that some of these new drugs might match the
stroke risk reduction of warfarin while being convenient,
having more predictable effects and a better safety
profile. These agents they have the potential to increase
adherence to therapy and to guidelines, and most importantly to the number of AF patients at reduced risk of
stroke.
Incomplete knowledge among healthcare professionals
The importance of patient empowerment has been
stressed already. Unless healthcare professionals are
equipped with a high knowledge of AF-patient management, it will remain almost impossible to engage patients in decision making and target setting for their own
management.
Benefits of current treatments to prevent stroke
The reasons for poor adherence to guidelines have been
reviewed in earlier sections. Many of these reasons are
rooted in the degree of understanding and concern that
physicians have about the safety and effectiveness of
warfarin. We have seen that doctors both underestimate
the benefits of warfarin and over estimate the risks. There
is also evidence that the safety of aspirin and effectiveness is overestimated by prescribers. This highlights an
urgent need for improved awareness and understanding
among physicians of the existing antithrombotic treatments and their essential role in the prevention of stroke
among AF patients.
The barriers of low awareness and knowledge among
healthcare professionals is also evident from survey data.
Physicians have reported that increased training and
availability of consultant advice or guidelines specifically
on managing anticoagulation therapy would increase
their willingness to prescribe warfarin.153
Evidence also suggests that healthcare professionals
need greater awareness of their patients’ ability to retain
information at the point of diagnosis, as well as greater
insight into the negative effects that the symptoms of AF
have on patients’ lives.
Provision of information
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need to understand the enormous
value
supplying
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written information covering critical advice and facts,
and that this is vital to ensure patient understanding and
engagement. Physicians also need to revisit this information in subsequent consultations to confirm and reinforce
patient understanding so that patients can become
involved in the making of informed decisions about their
care.
Physicians need also to recognised the negative impact
that symptoms are having on patients lives. Failure to do
this results in a feeling of abandonment and dismissal,
which will likely undermine efforts to educate and engage the patient in the management of AF, achieving the
opposite of patient empowerment.
Finally, efforts are required to ensure that always patients
receive consistent and accurate information and advice
that is uniformly specific to individual circumstances.
This is only possible if there is effective communication
between the various healthcare professionals involved in
the patient’s care.
Management of patients receiving warfarin
There is evidence to suggest that patients adhere to
warfarin therapy more closely when closely supervised
or routinely managed by a dedicated anticoagulation
service.152 However, there are great differences between
the many dedicated anticoagulation services provided
throughout the UK, but a distinct lack of information
on the effectiveness, quality and range of services that
they provide. Physicians need to become aware of the
strengths and limitations of their local anticoagulation
clinic, and remain mindful of alternatives such as home
testing. The roles of self-management and anticoagulation clinics is covered more closely at the end of this
chapter under Access to care and information.
Awareness of treatment innovations
Novel anticoagulants currently in advanced stages of
development may simplify the management of patients
with AF. As with any chronic intervention, however, highquality guidance and education for doctors, patients and
their carers will be essential. Healthcare professionals
will need to identify and manage eligible patients and
know how to deal with emergency situations. Increased
resources for education and rapid dissemination of information will allow faster introduction and uptake of new
therapies.
There is a large amount of information for patients to
absorb in one consultation with the physician. Physicians
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Inequity of access to effective
management
There is a considerable body of evidence that supports
the accuracy and reliability of self-testing.146,147,148,149
There is also high-level endorsement of home testing
from NICE which recommends that it is considered in
all AF patients in need of long-term anticoagulation, if
they would prefer self-management. The Department
of Health has committed to help fund home testing and
self-management is very much in line with government
strategy promoting patient choice and patient empowerment.
However, there are major disincentives for patients to
self-manage their warfarin treatment in the UK. The testing machines are not available on the NHS, preventing
their use among many patients who would benefit from
a high degree of involvement with their own treatment.
Furthermore, while the Department of Health has committed to funding the testing strips that the machines use,
many Primary Care Trusts (PCTs) are not currently funding
the strips in line with this commitment. The result is that
the cost falls to patients who should not have to face this
financial burden. Many patients simply can not afford
the strips and become failed by the system responsible
for their care. This situation also creates imbalance and
‘postcode prescribing’ where patients in one part of the
country are denied access to a therapy which is provided
routinely elsewhere.
There is need not only for agreed standards of care and
service from anticoagulation services, there is also need
for much greater consideration and support of home
testing for those patients likely to benefit. When the risks
and benefits of home testing are properly explained to
patients, nearly all (94%) find the option to be acceptable.147 In a study that investigated the role of self-testing,
87% of patients reported that they felt it to be straightforward and that they were confident with the results they
obtained. Research from outside the UK has also indicated that cost benefits might also be possible with home
testing.155
In further support of home testing and patient empowerment, there is general agreement among both primary
care physicians and specialists that anticoagulation
therapy is best managed by general practitioners, rather
than hospital doctors to ensure optimal access to, and
continuity, of care.153
Anticoagulation clinics – a potential educational
resource
Anticoagulation clinics may be run from a hospital or attached to a primary care practice. They have sometimes
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been considered the gold standard
of020
warfarin
managewww.anticoagulationeurope.org
152
ment helping to increase the time that a patient’s INR
values are within the target range, improve the overall
cost-effectiveness of therapy, increase patient adherence
and provide valuable information for both healthcare
professionals and patients.150,154 However, information
of the quality and range of services of these clinics in the
UK is poor. When the effectiveness of dedicated clinics is compared with home-monitoring, the results are
positive for self-testing. 149 Self-testing also avoids much
of the time and financial commitment required to make
frequent journeys to the clinic, and it frees patients from
feeling a need to remain close to their clinic at all times.
This can interfere considerably with daily life as patients
avoid travel and holidays because of such fears.
If patients are referred to an anticoagulation clinic,
communication between all the healthcare professionals
involved is crucial: assigning one part of patient care to
an external clinic can weaken the relationship between
the primary care physician and patient and may lead
to disruption of care if communication breaks down.152
Therefore, healthcare providers may need education and
support in ensuring a seamless transition between the
different strands in the patient pathway. As management
of patients receiving anticoagulants evolves, anticoagulation clinics will need to adapt.152 The organisation and
running of anticoagulation clinics might gain cost and
efficiency benefits through the adoption of technology.
Computer programs to calculate the required dose adjustment of warfarin have been found to perform just as
well as clinic staff.157,158 Anticoagulation clinic staff may
have an increasing role as educators and coordinators of
anticoagulation therapy, providing support and communications links for other healthcare providers.
Moves towards patient-centred care
Access to, and the quality of, management of patients
with AF is also likely to be greatly improved by a move
to more patient-centred care and patient empowerment.
Under current Department of Health policies, the consideration of patients’ needs, preferences and concerns
relating to overall health, rather than just to a specific
condition will become increasingly important. Although
a patient-centred approach is widely advocated, it is not
always implemented.159 Instead, health care is typically
centred on treating the disorder, rather than considering patients’ individual needs.159,160 There is evidence
that anticlotting therapy tailored to patients’ preferences
is more cost-effective than giving the same therapy to
every patient. 109 There is therefore a need to provide
physicians with further education on the benefits of patient-centred care and with support in implementing this
approach locally.
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Interruptions in the continuum of
patient care
Continuity of care, involving timely communication between healthcare providers, is essential for high-quality
care. As the provision of health care often involves several different service providers, continuity of care is defined
as ‘coherent health care with a seamless transition over
time between various providers in different settings’.162
By empowering patients and adopting a patient-centred
approach to management, many factors that interrupt
the continuum of care can be identified and eliminated.
Clinical research supports the need for an optimised
continuum of care. In one paper, the defining characteristics of an ideal continuum were established; the seven
Cs) of optimal continuity of care.162
• Regular contact between patients and healthcare
providers.
• Collaboration between healthcare professionals and
patients in educating and ‘empowering’ the patient.
• Communication between healthcare providers.
• Coordination of the multidisciplinary teams involved,
with clear identification of different roles.
• Contingency plans in the form of access to
healthcare professionals out of hours to answer
questions and address concerns.
• Convenience – achieved, for example, by avoiding
the need for patients to keep repeating information
and by considering home monitoring.
• Consistency of the advice provided by different
professionals and adherence to clinical practice
Guidelines.
The close monitoring required in patients receiving warfarin therapy can be problematic in ensuring continuity of
care. When patients are transferred to other healthcare
providers or to different settings, such as during hospitalisation or at discharge from hospital, critical information can be lost. Comprehensive, timely and appropriate
discharge information is essential – possibly in some
portable format 163 – so that the primary care practice
has all it needs for appropriate follow-up care. Insufficient discharge information can contribute to hospital
readmission.164 Education of carers also plays a key role
in the success of therapy, and the availability of a healthcare provider to answer questions and address concerns
is likely to improve continuity of care.
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Conflicting guidelines
and GP targets
www.anticoagulationeurope.org
When guidelines provide conflicting information or when
outcomes rewards fail to motivate treatment in accordance with guidelines, there is significant opportunity for
patient management that falls short of what is ideal. In
the UK, healthcare providers have a choice of two conflicting sets of authoritative guidelines; those from NICE
and those from ESC.
It is essential that the planned review of the existing NICE
2006 guidelines are updated to reflect not only the existing ESC guidelines, but also to reflect improvements that
the authors of the ESC guidelines are already considering.
It is also necessary to change the current QOF scheme
that rewards physicians for achieving targeted patient
outcomes. In the previous chapter, this topic was addressed in more detail, but the current scheme provides
virtually no motivation for GPs to put patients on warfarin in accordance with either the NICE 2006 or the
ESC 2010 guidelines. Proposed changes to this scheme
would help eliminate this barrier to effective AF patient
management.
Summary of current challenges
In summary, numerous challenges remain in the prevention of stroke in patients with AF. Increased detection
of AF by physicians is vital, and improved education is
needed among patients and healthcare professionals on
the benefit-to-risk profile of aspirin and warfarin, and on
the optimum management of patients receiving warfarin. Healthcare professionals need to be aware of new
anticoagulants and other therapeutic strategies that are
emerging, as well as advances in the treatment of the underlying AF. It is also vitally important to encourage patient empowerment and patient-centred care and ensure
equity of access to advances such as self-management.
Finally, improved adherence to guidelines, consistent
recommendations between guidelines and collaborative
approaches to the development of revised guidelines are
essential, as are revisions to schemes that exist to motivate GP to achieve outcome targets among AF patients.
All of these factors will contribute to the prevention of
stroke in patients with AF.
The AF Report
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020 8289 6875
www.anticoagulationeurope.org
Chapter 9 - New treatments in development
Key points
• Practical and perceived drawbacks of warfarin are
limiting its potential to prevent stroke
• alternative anticoagulants in development aim to
offer efficacy, safety and convenience, without need
for monitoring or dose adjustment
• Three oral anticoagulants are in the final stages of
development for the prevention of stroke in AF
• Promising minimally-invasive procedures have also
been developed for correcting abnormal heart
rhythms and eliminating the source of AF-related
blood clots
Limitations of warfarin and aspirin restrict their use and
effectiveness in the prevention of stroke in patients with
AF. These limitations have led to an ongoing search for
alternative effective and convenient therapies. In addition, there have been developments in anti-arrhythmic
drugs used to treat AF. These developments are discussed in more detail below.
Anticoagulant agents
There are many challenges involved in the effective
use of current anticoagulants to prevent stroke. Taken
together, they point clearly to what might be the ideal
characteristics of an anticoagulant for long-term use in
AF.165
Warfarin can be very effective, is relatively simple to take,
and is somewhat safer than many physicians appear to
believe, but it does not fulfil the remaining criteria for
an ideal anticoagulant. Warfarin interacts with food and
other drugs in a way that can lead to blood levels far
outside a very narrow therapeutic window. Consequently,
warfarin requires frequent monitoring and dose adjustments. When monitoring and adjustment are lax, both
the effectiveness and safety of warfarin are compromised.
Understandably, there has been a long search for alternative anticoagulants. The clotting process is a complicated cascade of biological reactions providing many
potential targets for a new drug. Yet it has taken decades
of research to uncover new compounds that are effective in tackling some of these targets. The agents that
are most advanced in their development act on single
proteins in the coagulation pathway; either clotting factor
Xa (pronounced ‘ten A’) which is involved in the amplification of the clotting response, or on thrombin which
enables the final step of the clotting process to take
place.165 Today, development of a handful of new oral
anticoagulants has advanced to human trials in large
numbers of patients.
The below table summarises the new anticoagulation
agents which have filed, or which plan imminently to file,
applications for European regulatory approval. These
and other agents in the final stage of development are
discussed below.
• As effective as warfarin
• A large therapeutic window (a wide separation
between blood levels that reduce the risk of a blood
clot and those that substantially increase the risk of
bleeding)
• A good safety profile in a wide range of patients,
including the elderly
• A low tendency to interact with food and other drugs
• No need for regular monitoring and dose adjustment
• Easy and simple to take (i.e., by mouth in pill or
capsule form on daily basis)
The AF Report
41
www.afa.org.uk
020 8289 6875
c
New anticoagulant agents offer potential alternative to warfarin in some patientswww.anticoagulationeurope.org
Agent
Commercial Name Class
Current indications Status of AF indication
Rivaroxaban
Xarelto
Direct factor Xa inhibitor
VTEa
AFb
Licensed Dec-2011
Apixaban
Eliquis
Direct factor Xa inhibitor
VTEa
Filed 2011
Dabigatran
Pradaxa
Direct thrombin inhibitor
VTEa
AFb
Licensed 2011
a
b
c
The prevention of venous thromboembolism in adults after hip or knee replacement
To prevent strokes and the formation of clots in adults who have an abnormal heart beat called ‘non-valvular
atrial fibrillation’ and are considered to be at risk of stroke
Accurate at Feb 2012
Oral factor Xa inhibitors
Clotting factor Xa has few functions in the body outside
coagulation, making it an excellent target for potential
new anticoagulants as this may result in fewer side effects.166 Inhibition of factor Xa inhibits thrombin generation, while allowing existing thrombin to continue its vital
role in blood clotting.166 Oral inhibitors of factor Xa in
late-stage development include rivaroxaban, apixaban
and edoxaban. Two factor Xa inhibitors are currently
licensed in the UK by the Medicines and Healthcare
products Regulatory Agency (MHRA); rivaroxaban,170 and
apixaban.167 Both are available Europe-wide following
authorisation from the European Medicines Agency. Both
agents are available for the prevention of clotting problems in the veins in adults after hip or knee replacement
surgery. For this indication, called venous thromboembolism (VTE), rivaroxaban is taken orally, once daily at a
fixed dose; apixaban is taken orally, twice daily at a fixed
dose.
ROCKET-AF was a randomised, double-blind study that
compared the efficacy and safety of rivaroxaban 20 mg
once daily with warfarin for the prevention of stroke in
approximately 14,000 high-stroke-risk patients with
AF.168,169
Apixaban
Two pivotal studies of apixaban have recently released
results. The AVERROES study compared apixaban with
aspirin in 5,599 AF patients who were unable to take
warfarin. The study was stopped early having demonstrated clearly that apixaban was associated with a significant reduction in strokes when compared with aspirin.
A second pivotal trial, ARISTOTLE, compared apixaban
with warfarin in over 18,000 AF patients. Results from
this trial show that apixaban was superior to warfarin
in preventing stroke or systemic embolism, caused less
bleeding, and resulted in lower mortality.
Edoxaban
Unlike warfarin, rivaroxaban and apixaban have a wide
therapeutic window and do not require routine monitoring. The manufactures of rivaroxaban have also now
submitted additional indications for licence, including
stroke prevention in patients with AF and the treatment
of deep vein thrombosis. The manufacturers of apixaban
have announced plans to make regulatory filings in
2011 for stroke prevention in AF patients.
Pivotal studies of edoxaban have yet to complete but
earlier trials indicated that AF patients taking edoxaban
had a similar incidence of bleeding to those assigned to
warfarin.172 A pivotal phase III study (ENGAGE- AF TIMI
48) is underway to demonstrate the safety and efficacy
profile of different edoxaban doses compared to
warfarin.171
Rivaroxaban
Indirect factor Xa inhibitors
The pivotal clinical study of rivaroxaban is called
ROCKET AF.168,169 The results of the study showed that AF
patients taking rivaroxaban had a comparable risk
of stroke and a similar risk of bleeding compared to
patients taking warfarin.169
Another group of factor Xa inhibitors are under investigation. These agents, instead of acting directly, limit the activity of factor Xa via antithrombin. Among these indirect
factor Xa inhibitors, biotinylated idraparinux is the most
studied and the only example to have been involved in
a late-stage clinical study. Unlike the direct Factor Xa
42
The AF Report
www.afa.org.uk
inhibitors above, biotinylated idraparinux is administered
by subcutaneous injection.165 A study called BOREALISAF was evaluating whether subcutaneous biotinylated
idraparinux administered once a week was at least as effective as warfarin for the prevention of stroke in patients
with AF.171 However, the trial was halted by the sponsor.
This is the second trial of biotinylated idraparinux to have
been stopped early. However, unlike a predecessor BOREALIS-AF was not stopped because of a safety concern.
This earlier trial, which used a different formulation of the
drug, was stopped as a result of bleeding concerns.
Thrombin inhibitors
Dabigatran
Dabigatran etexilate directly inhibits the action of
thrombin, blocking the final step of the clotting cascade
which converts fibrinogen to fibrin. Similar to apixaban
and rivaroxaban, throughout Europe dabigatran has
been approved for the prevention of VTE in adults after
total hip replacement or total knee replacement surgery.173 The pivotal, late-stage clinical study of dabigatran is called RE-LY, which compared the efficacy and
safety of dabigatran with warfarin in 18,113 AF patients.
RE-LY compared two doses of dabigatran, taken orally,
twice daily, to warfarin. The lower dose was associated
with a stroke rate comparable to that seen with warfarin,
but with a lower rate of major bleeds. The higher dose
resulted in a significantly lower rate of stroke compared
to warfarin and a similar rate of major bleeds.174 Further
studies of dabigatran and other direct thrombin inhibitors
are ongoing.176,55
Antiplatelet agents
Clopidogrel is an inhibitor of platelet aggregation. Reduced platelet aggregation reduces the risk of a blood
clot forming. In a study called ACTIVE-A, clopidogrel in
combination with aspirin was compared to aspirin alone
for the prevention of stroke in AF patients for whom
warfarin therapy was unsuitable. While clopidogrel in
combination with aspirin significantly reduced the risk of
stroke in patients with AF, it was also associated with a
significantly greater rate of major bleeding.177
Additional studies are under way to assess the efficacy
and safety of clopidogrel for stroke prevention in patients
with AF.171 Clopidogrel is currently licensed for other
indications including the prevention of atherothrombotic
events in patients suffering from heart attack.185
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020 8289 6875
Alternative strategies
www.anticoagulationeurope.org
Current strategies are focused on drugs that target the
process of clot formation. However, other strategies are
emerging for patients with AF. These include:178
• Drugs and procedures that target AF itself
• Drugs and procedures to control heart rhythm and
heart rate
• Drugs and procedures to prevent blood clots
reaching the brain
New rate and rhythm control drugs
In rhythm control, drugs are used to restore and maintain
the sinus rhythm of the heart; in rate control, drugs are
used to maintain a suitably low heart rate. Examples of
drugs used for rhythm or rate control include amiodarone, digoxin and beta-blockers.
Dronedarone is a new anti-arrhythmic drug licensed
for use in clinically stable patients with non-permanent
atrial fibrillation, to prevent recurrence of AF or to lower
the pulse rate. In trials dronedarone has been shown to
reduce the incidence of death or hospitalisation due to
cardiovascular events compared with placebo.188
Non-pharmacological methods
Non-pharmacological interventions for stroke prevention
in AF concentrate on eliminating the AF itself; stopping
potentially harmful blood clots from reaching the brain,
or by preventing the formation of clots.
Non-pharmacological management of
abnormal heart rhythm
There are numerous non-pharmacological methods for
the management of abnormal heart rhythm.178
These include:
• Electrical cardioversion: the process by which an
abnormally fast heart rate or disturbance in heart
rhythm is terminated by the delivery of an electric
current to the heart at a specific moment in the
heart cycle
• Radiofrequency (RF) catheter ablation: a minimallyinvasive procedure used to correct a faulty electrical
pathway in the heart
• Non-RF ablation: open surgical or minimallyinvasive procedures that correct the faulty electrical
pathways from the heart
43
www.afa.org.uk
• Left atrial appendage (LAA) occlusion: minimallyinvasive procedure that either prevents clots from
forming or prevents them from leaving the site of
formation in the heart
Current data suggest that catheter ablation is more
effective than anti- arrhythmic drug therapy in maintaining normal heart rhythm.179 Whether or not this intervention affects the incidence strokes requires further evaluation in clinical trials.
Procedural interventions to reduce
stroke risk
One procedural approach to preventing stroke in AF patients seeks to remove an anatomical contributor to clot
formation. More than 90% of blood clots in AF patients
form in the left atrial appendage (LAA) of the heart.178
The LAA is a small sac behind an opening the wall of
the left atrium. It has been suggested that AF particularly
degrades the normal flow of blood in the LAA, allowing
clot formation.
Sealing the left atrial appendage, isolating it from the
main atrial chamber, may therefore prove to be an effective and permanent way to reduce the risk of blood clots
and stroke. Several new occlusion devices have been
developed that block the LAA. Such devices are designed
to be placed permanently, sealing the opening of the
LAA. Once in place, potentially harmful blood clots no
longer have opportunity to form in the LAA and any
thrombotic material in the LAA is prevented from entering
the bloodstream and causing stroke.180,181 One of these
devices, Watchman, recently received approval for use in
Europe.181 The results of a recently published trial, PROTECT-AF, showed that closure of the LAA with Watchman
was comparable to warfarin for stroke prevention. The
study authors noted caution, having observed an overall
increase in the rate of adverse events in the LAA group
compared to warfarin. However, unlike drugs, devicerelated interventions frequently demonstrate substantial
safety improvements associated with increased operator
experience. A subsequent paper from an extension of the
same study investigated this effect. A significant reduction
in safety events was observed during the second half of
the study period compared to the first. It was also noted
that the impact of these safety events, as defined by significant disability or death, was statistically superior in the
Watchman group compared with the warfarin group. The
authors concluded that closure of the LAA might provide
an alternative strategy to chronic warfarin therapy for
stroke prophylaxis in patients with AF.182,183
44
Summary
020 8289 6875
www.anticoagulationeurope.org
To summarise, there are several pharmacological agents
in development for use in patients with AF, including the
new oral anticoagulants rivaroxaban, dabigatran and
apixaban. Minimally-invasive device interventions for the
management of arrhythmias and the reduction of stroke
risk are also being developed.
Valuable insights into the impact of these new therapies
on the prevention of stroke in patients with AF can be
gained from real-life registries. A number of registries of
AF patients are in existence, most of which are country
specific or focused on North America.
A new global registry has now been established, the
Global Anticoagulant Registry in the FIELD (GARFIELD).
GARFIELD will prospectively follow 50,000 newly-diagnosed AF patients and 5,000 patients with previouslydiagnosed AF, over six years.192 Patients will be included
and followed, regardless of whether or not they receive
appropriate therapy. The GARFIELD registry will document details such as the risk factors, treatment patterns
and clinical events associated with AF, and will provide
a picture of the real-life global burden of the condition.
It is also hoped that GARFIELD will show how the new
advances in therapy can contribute to the prevention of
stroke in patients with AF.186
It is hoped that the availability of new therapy options,
together with a greater understanding of their impact
on the burden of stroke, will pave the way for better
management of patients with AF.
The AF Report
www.afa.org.uk
020 8289 6875
www.anticoagulationeurope.org
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The AF Report
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The AF Report
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www.afa.org.uk
www.anticoagulationeurope.org
Atrial Fibrillation: Preventing A Stroke Crisis
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Calculate your personal risk
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This report was developed by the Atrial Fibrillation Association (AFA) and AntiCoagulation Europe (ACE), both of which are charities engaged
in patient advocacy, support and education. The report content is based upon a Working Group Report prepared by Action for Stroke Prevention.
This revision has been updated and rewritten specifically for online access by UK patients and those who care for them. Development of this
report was supported by an unrestricted grant provided to the AFA and ACE by Bayer Healthcare. © Copyright AFA and ACE 2011.